{"entity": "researcher", "timestamp": "2026-07-14T01:22:30.482Z", "family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "affiliations": ["Section of Neurology, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43"}}, "publications": [{"entity": "publication", "iuid": "310db69525be40ed9f4e569c00320568", "links": {"self": {"href": "https://publications.scilifelab.se/publication/310db69525be40ed9f4e569c00320568.json"}, "display": {"href": "https://publications.scilifelab.se/publication/310db69525be40ed9f4e569c00320568"}}, "title": "Ultra-large virtual screening unveils potent agonists of the neuromodulatory orphan receptor GPR139.", "authors": [{"family": "Cabeza de Vaca", "given": "Israel", "initials": "I", "orcid": "0000-0002-6208-1091", "researcher": {"href": "https://publications.scilifelab.se/researcher/65628edbdaa448b8ab37d5eb4e100aee.json"}}, {"family": "Trapkov", "given": "Boris", "initials": "B", "orcid": "0000-0003-1245-888X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6dc796a7e85b4849ae92b2d3ce13a885.json"}}, {"family": "Shen", "given": "Ling", "initials": "L"}, {"family": "Vo", "given": "Duy Duc", "initials": "DD"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X", "orcid": "0000-0002-9461-8682", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f307c88103d43b1b0b893fa59a8e828.json"}}, {"family": "Yang", "given": "Yunting", "initials": "Y"}, {"family": "Pezeshki", "given": "Mitra", "initials": "M", "orcid": "0009-0001-0155-7463", "researcher": {"href": "https://publications.scilifelab.se/researcher/e51c7fe034b9477996d92c2dbddf6f21.json"}}, {"family": "Zhang", "given": "Xuehan", "initials": "X"}, {"family": "B\u00e4llgren", "given": "Frida", "initials": "F"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "Tarnovskiy", "given": "Andrii V", "initials": "AV"}, {"family": "Radchenko", "given": "Dmytro S", "initials": "DS", "orcid": "0000-0001-5444-7754", "researcher": {"href": "https://publications.scilifelab.se/researcher/df4077c366bc4f4a8b422762c0be9cfe.json"}}, {"family": "Moroz", "given": "Yurii S", "initials": "YS", "orcid": "0000-0001-6073-002X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f8586d3b69b4782bed34192411a02e5.json"}}, {"family": "Br\u00e4uner-Osborne", "given": "Hans", "initials": "H"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Kihlberg", "given": "Jan", "initials": "J", "orcid": "0000-0002-4205-6040", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9805d4f39cc48f79a6e6ba076917021.json"}}, {"family": "Liu", "given": "Zhi-Jie", "initials": "ZJ", "orcid": "0000-0001-7279-2893", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5198c9a2924467bb85b451b99f381b.json"}}, {"family": "Hauser", "given": "Alexander Sebastian", "initials": "AS", "orcid": "0000-0003-1098-6419", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d10bc754dbc4fb49ae26994ab9fcff1.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7d91087358e46e38bb1b7110dc0b214.json"}}], "type": "journal article", "published": "2025-12-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723"}, "abstract": "The orphan G protein-coupled receptor (GPCR) GPR139 attracts interest as a target for neuropsychiatric disorders. Whereas the physiological functions of GPR139 remain elusive, a high-resolution receptor structure is now available. To assess whether structural information enables ligand discovery, we computationally dock 235 million compounds to the GPR139 binding site. Of 68 top-ranked compounds evaluated experimentally, five are full agonists with potencies ranging from 160 nM to 3.6 \u00b5M. Structure-guided optimization identifies one of the most potent GPR139 agonists, and a cryo-EM structure of the receptor-ligand complex confirms the predicted binding mode. Functional characterization provides insights into GPR139 signalling, and one agonist elicits behavioural effects in mice. We also explore the potential to replace experimental structure determination with the deep-learning method AlphaFold3, revealing a limited capability of artificial intelligence to model receptor-ligand interactions for understudied GPCRs. The results demonstrate how high-resolution GPCR structures combined with large-library docking can accelerate drug discovery.", "doi": "10.1038/s41467-025-66845-y", "pmid": "41365886", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-025-66845-y"}], "notes": [], "created": "2025-12-15T10:13:02.964Z", "modified": "2025-12-15T10:13:04.219Z"}, {"entity": "publication", "iuid": "2e917c797feb476e8c34b4c4e6e2a631", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e917c797feb476e8c34b4c4e6e2a631.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e917c797feb476e8c34b4c4e6e2a631"}}, "title": "The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain.", "authors": [{"family": "Gerlach", "given": "Jule", "initials": "J"}, {"family": "Pireddu", "given": "Paola", "initials": "P"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Wetzel", "given": "Simon", "initials": "S", "orcid": "0000-0003-1831-0376", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddd21b38f82f4624a40679559339c845.json"}}, {"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}}, {"family": "Milenkovic", "given": "Dusanka", "initials": "D", "orcid": "0000-0003-0151-8760", "researcher": {"href": "https://publications.scilifelab.se/researcher/7667a08efad244b88892a772f51ccf50.json"}}, {"family": "Nolte", "given": "Hendrik", "initials": "H"}, {"family": "da Silva Rodrigues", "given": "Fernanda", "initials": "F"}, {"family": "Branzell", "given": "Niclas", "initials": "N", "orcid": "0009-0009-3472-6903", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bde4ad10f0146379233871ea29ea918.json"}}, {"family": "Kaya", "given": "Ibrahim", "initials": "I", "orcid": "0000-0003-3345-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/99a00a900df8419f96fafa97344e56ea.json"}}, {"family": "Villegas", "given": "Rodolfo Garcia", "initials": "RG"}, {"family": "Rubalcava-Gracia", "given": "Diana", "initials": "D", "orcid": "0000-0002-4615-7375", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b075c43c2244ee9a26fae7b09d523a.json"}}, {"family": "Alsina", "given": "David", "initials": "D"}, {"family": "Feederle", "given": "Regina", "initials": "R", "orcid": "0000-0002-3981-367X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c19111a0c7af42d4a22b7221e4426909.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}, {"family": "Langer", "given": "Thomas", "initials": "T"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.json"}}], "type": "journal article", "published": "2025-10-06", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "16", "issue": "1", "pages": "693", "issn-l": "2041-4889"}, "abstract": "The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations in the genes encoding these proteins have been linked to severe disorders, including Parkinson's disease and amyotrophic lateral sclerosis. In cultured cells, a small fraction of CHCHD2 and CHCHD10 oligomerize to form a high molecular weight complex of unknown function. Here, we generated a whole-body Chchd2 knockout mouse to investigate the in vivo role of CHCHD2 and its protein complex. We show that CHCHD2 is crucial for sustaining full motor capacity, normal striatal dopamine levels, and lipid homeostasis in the brain of adult male mice. We also demonstrate that in mouse tissues, CHCHD2 and CHCHD10 exist exclusively as a high molecular weight complex, whose levels are finely tuned under physiological conditions. In response to mitochondrial dysfunction, the abundance and size of the CHCHD2-CHCHD10 complex increase, a mechanism conserved across different tissues. Although the loss of CHCHD2 does not abolish CHCHD10 oligomerization, it enhances cell vulnerability to mitochondrial stress, suggesting that CHCHD2 is protective against mitochondrial damage. Our findings uncover the role of CHCHD2 in preserving tissue homeostasis and provide important insights into the involvement of the CHCHD2-CHCHD10 complex in human diseases.", "doi": "10.1038/s41419-025-08030-z", "pmid": "41053020", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12501252"}, {"db": "pii", "key": "10.1038/s41419-025-08030-z"}], "notes": [], "created": "2025-11-21T09:46:18.171Z", "modified": "2025-11-27T13:31:05.879Z"}, {"entity": "publication", "iuid": "2110c851b57d4479b99eb959647a15e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2110c851b57d4479b99eb959647a15e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2110c851b57d4479b99eb959647a15e4"}}, "title": "High Cerebrospinal DOPA Decarboxylase Level Predicts Cognitive Decline in Parkinson's Disease.", "authors": [{"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Paslawski", "given": "Wojciech", "initials": "W", "orcid": "0000-0003-2141-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce039c7e5e774d66a8c0331a3c990ccc.json"}}, {"family": "Khosousi", "given": "Shervin", "initials": "S"}, {"family": "Markaki", "given": "Ioanna", "initials": "I", "orcid": "0000-0003-3328-5746", "researcher": {"href": "https://publications.scilifelab.se/researcher/929b8fea137e410b96d1a6754690c447.json"}}, {"family": "Nalls", "given": "Michael A", "initials": "MA"}, {"family": "Singleton", "given": "Andrew B", "initials": "AB"}, {"family": "Iwaki", "given": "Hirotaka", "initials": "H"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2025-09-24", "journal": {"title": "Mov Disord Clin Pract", "issn": "2330-1619", "issn-l": null}, "abstract": "DOPA decarboxylase (DDC) in cerebrospinal fluid (CSF) is an emerging Parkinson's disease (PD) biomarker, but its association with nonmotor symptoms is unclear.\n\nWe aimed to determine if baseline DDC was associated with future cognitive decline in PD.\n\nWe correlated baseline CSF DDC, detected using the proximity extension assay, with Montreal Cognitive Assessment (MoCA) score using longitudinal data from 3 cohorts: Biopark, PPMI, and PDBP.\n\nDDC was significantly associated with cognitive decline in both the Biopark cohort (P-value < 0.0001) and the PDBP/PPMI cohorts (P-value < 0.0001). The results were still significant after correcting for levodopa-equivalent daily dose in the Biopark cohort (P-value < 0.0001) and when the analysis was restricted to the de novo subjects, both in Biopark (P-value: 0.0065) and PPMI (P-value<0.0001) cohorts.\n\nCSF DDC is a potential biomarker for the prediction of cognitive decline in PD patients.", "doi": "10.1002/mdc3.70367", "pmid": "40990085", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-24T22:25:28.475Z", "modified": "2025-11-24T22:25:28.974Z"}, {"entity": "publication", "iuid": "769397eccc3044d2b50395eaade60782", "links": {"self": {"href": "https://publications.scilifelab.se/publication/769397eccc3044d2b50395eaade60782.json"}, "display": {"href": "https://publications.scilifelab.se/publication/769397eccc3044d2b50395eaade60782"}}, "title": "Enduring modulation of dorsal raphe nuclei regulates (R,S)-ketamine-mediated resilient stress-coping behavior.", "authors": [{"family": "Camargo", "given": "Anderson", "initials": "A"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Appleton", "given": "Ellen", "initials": "E"}, {"family": "Branzell", "given": "Niclas", "initials": "N"}, {"family": "Doyon", "given": "Daniel", "initials": "D"}, {"family": "Giovenzana", "given": "Mattia", "initials": "M", "orcid": "0009-0002-1384-3413", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2cd71f47b7a40d7b996da916888798b.json"}}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X", "orcid": "0000-0002-9461-8682", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f307c88103d43b1b0b893fa59a8e828.json"}}, {"family": "Dautan", "given": "Daniel", "initials": "D"}, {"family": "Andren", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "Mol. Psychiatry", "issn": "1476-5578", "volume": "30", "issue": "6", "pages": "2504-2516", "issn-l": "1359-4184"}, "abstract": "Ketamine may be a novel pharmacologic approach to enhance resilience and protect against stress-related disorders, but the molecular targets underlying this response remain to be fully characterized. The multifunctional protein p11 is crucial in the pathophysiology of depression and antidepressant responses. However, it is still unclear whether p11 plays a role in the pro-resilience effects induced by ketamine. Here, we demonstrated that prophylactic administration of ketamine buffers passive stress-induced maladaptive phenotypes induced by chronic stress exposure. Spatial neurotransmitter and metabolite analysis revealed that prophylactic ketamine was also effective in blunting stress-induced disturbances of tryptophan metabolism in dorsal raphe nuclei (DRN). Additionally, we demonstrated that ketamine prevented chronic restraint stress-induced p11 reduction in DRN, a highly p11-enriched region. Furthermore, we provide novel evidence indicating that p11 deficiency regulates susceptibility to stress-induced depression-related phenotypes, and these behavioral maladaptations are dependent, at least in part, on p11 function in serotonergic neurons. Spatial neurotransmitter and metabolite analysis also showed a reduction of tryptophan and dopamine metabolism in DRN of serotonergic p11-deficient mice. Viral-mediated downregulation of p11 within DRN induced a stress-susceptible phenotype. Finally, our results also unveiled that the ability of ketamine to elicit a pro-resilience response against stress-induced maladaptive phenotypes was occluded when p11 was selectively deleted in serotonergic neurons. Altogether, we showed a previously unexplored role of the DRN circuit in regulating stress susceptibility and resilience-enhancing actions of ketamine.", "doi": "10.1038/s41380-024-02853-6", "pmid": "39592824", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12092261"}, {"db": "pii", "key": "10.1038/s41380-024-02853-6"}], "notes": [], "created": "2025-11-21T09:46:25.178Z", "modified": "2025-11-21T09:46:25.384Z"}, {"entity": "publication", "iuid": "859055d5fe394252bb2808f0d2a3394e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/859055d5fe394252bb2808f0d2a3394e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/859055d5fe394252bb2808f0d2a3394e"}}, "title": "ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model.", "authors": [{"family": "Akkuratov", "given": "Evgeny E", "initials": "EE"}, {"family": "Sorrell", "given": "Francesca", "initials": "F"}, {"family": "Picton", "given": "Laurence D", "initials": "LD"}, {"family": "Sousa", "given": "Vasco C", "initials": "VC"}, {"family": "Paucar", "given": "Martin", "initials": "M", "orcid": "0000-0003-3735-1480", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc592904eb5402ea48a624471d4b939.json"}}, {"family": "Jans", "given": "Daniel", "initials": "D", "orcid": "0000-0002-6356-9742", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe197a6a51a946a7a6c01f4c9c6cce08.json"}}, {"family": "Svensson", "given": "Lill-Britt", "initials": "LB"}, {"family": "Lindskog", "given": "Maria", "initials": "M", "orcid": "0000-0001-9484-1983", "researcher": {"href": "https://publications.scilifelab.se/researcher/1592b4e2f1354bdd8b35f384dcac78c2.json"}}, {"family": "Fritz", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-9722-7425", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec61383c813443f29dea569ea935b284.json"}}, {"family": "Liebmann", "given": "Thomas", "initials": "T"}, {"family": "Sillar", "given": "Keith T", "initials": "KT"}, {"family": "Rosewich", "given": "Hendrik", "initials": "H", "orcid": "0000-0003-4692-5511", "researcher": {"href": "https://publications.scilifelab.se/researcher/fffad5ec5d2d48a78573e71d7ba3c2dd.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Miles", "given": "Gareth B", "initials": "GB"}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal article", "published": "2025-04-03", "journal": {"title": "Brain", "issn": "1460-2156", "volume": "148", "issue": "4", "pages": "1099-1105", "issn-l": "0006-8950"}, "abstract": "Mutations in the gene encoding the alpha3 Na+/K+-ATPase isoform (ATP1A3) lead to movement disorders that manifest with dystonia, a common neurological symptom with many different origins, but for which the underlying molecular mechanisms remain poorly understood. We have generated an ATP1A3 mutant mouse that displays motor impairments and a hyperexcitable motor phenotype compatible with dystonia. We show that neurons harbouring this mutation are compromised in their ability to extrude raised levels of intracellular sodium, highlighting a profound deficit in neuronal sodium homeostasis. We show that the spinal motor network in ATP1A3 mutant mice has a reduced responsiveness to activity-dependent rises in intracellular sodium and that this is accompanied by loss of the Na+/K+-ATPase-mediated afterhyperpolarization in motor neurons. Taken together, our data support that the alpha3 Na+/K+-ATPase is important for cellular and spinal motor network homeostasis. These insights suggest that it may be useful to consider ways to compensate for this loss of a critical afterhyperpolarization-dependent control of neuronal excitability when developing future therapies for dystonia.", "doi": "10.1093/brain/awae373", "pmid": "39533828", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11967811"}, {"db": "pii", "key": "7896743"}], "notes": [], "created": "2024-11-18T09:02:43.236Z", "modified": "2025-11-12T11:33:48.972Z"}, {"entity": "publication", "iuid": "4d12b06a01ae4f7aa582051ac121185b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4d12b06a01ae4f7aa582051ac121185b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4d12b06a01ae4f7aa582051ac121185b"}}, "title": "Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [11C]PBR28 PET.", "authors": [{"family": "Wallin", "given": "Johan", "initials": "J", "orcid": "0000-0003-0490-9900", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f513ad777614e57a30ce641b9c436ae.json"}}, {"family": "Forsberg", "given": "Anton", "initials": "A", "orcid": "0000-0001-8790-3306", "researcher": {"href": "https://publications.scilifelab.se/researcher/e825af97d4ac433198d14d2c20826ed2.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2025-04-00", "journal": {"title": "Mov Disord", "issn": "1531-8257", "volume": "40", "issue": "4", "pages": "739-744", "issn-l": null}, "abstract": "Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD).\n\nThe objective was to examine the safety and tolerability of montelukast, a cysteinyl-leukotriene receptor1 and GPR17 antagonist, in patients with PD. Secondary outcomes were target engagement, effects on PD signs/symptoms, and central neuroinflammation.\n\nFifteen PD patients were recruited to a 12-week open-label trial of 20 mg bi-daily montelukast treatment. Patients underwent ratings with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the Montreal Cognitive Assessment (MoCA), Beck's Depression Inventory (BDI), Parkinson's Disease Questionnaire-39 (PDQ-39), [11C]PBR28-PET, and lumbar punctures before and during montelukast treatment.\n\nAll patients completed the study. Three patients reported loose stool. No serious adverse events related to treatment were reported. MDS-UPDRS-Total scores improved by 6.9 points. Very low levels of montelukast were detected in all cerebrospinal fluid (CSF) samples and resulted in a reduction in inflammation/metabolism markers. [11C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast.\n\nMontelukast crosses the blood-brain barrier at very low levels and is well tolerated and safe in PD patients. Preliminary effects on neuroinflammation and clinical scores motivate a future randomized controlled trial (RCT) in PD. \u00a9 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.", "doi": "10.1002/mds.30144", "pmid": "39912596", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12006882"}], "notes": [], "created": "2025-11-18T12:16:32.491Z", "modified": "2025-11-18T12:16:32.623Z"}, {"entity": "publication", "iuid": "de5f9b658ce74f6096b9c352ea946d5b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de5f9b658ce74f6096b9c352ea946d5b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de5f9b658ce74f6096b9c352ea946d5b"}}, "title": "SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion.", "authors": [{"family": "Christ", "given": "Wanda", "initials": "W", "orcid": "0000-0003-3886-5248", "researcher": {"href": "https://publications.scilifelab.se/researcher/38fe3a44fdb547b885cce5b6f490b2bc.json"}}, {"family": "Kapell", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-9304-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cffd944f88e54ed6a910183ba49ef656.json"}}, {"family": "Sobkowiak", "given": "Michal J", "initials": "MJ", "orcid": "0000-0003-2932-1994", "researcher": {"href": "https://publications.scilifelab.se/researcher/14f1eb990edf472cac56f24d7cae330c.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Evertsson", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Sork", "given": "Helena", "initials": "H", "orcid": "0000-0002-5390-4420", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5d08dad4f2d4ee0a3e3a8f060383da5.json"}}, {"family": "Saher", "given": "Osama", "initials": "O"}, {"family": "Bazaz", "given": "Safa", "initials": "S"}, {"family": "Gustafsson", "given": "Oskar", "initials": "O"}, {"family": "Cardenas", "given": "Eduardo I", "initials": "EI"}, {"family": "Villa", "given": "Viviana", "initials": "V"}, {"family": "Ricciarelli", "given": "Roberta", "initials": "R"}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/7468c415a46645a3a4c3d28badcff954.json"}}, {"family": "Bergquist", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4597-041X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d745034529f3423abbea230b4e586d20.json"}}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Malm", "given": "Tarja", "initials": "T", "orcid": "0000-0002-9530-7472", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1ab3c9695424308b07c375901a089f4.json"}}, {"family": "Espay", "given": "Alberto J", "initials": "AJ"}, {"family": "Pernemalm", "given": "Maria", "initials": "M", "orcid": "0000-0003-4624-031X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f15f303cb2044cfa81719700137e3603.json"}}, {"family": "Lind\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "El Andaloussi", "given": "Samir", "initials": "S", "orcid": "0000-0003-4468-9113", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd1036a42043441da3e444f4eac58010.json"}}, {"family": "Ezzat", "given": "Kariem", "initials": "K", "orcid": "0000-0003-4186-0675", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f2f1d3d8a5d467c8fc3b95388e4c606.json"}}], "type": "journal article", "published": "2024-11-20", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "22", "pages": "4095-4104", "issn-l": "1948-7193"}, "abstract": "The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogeneous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as APLP1 (amyloid \u03b2 precursor like protein 1), ApoE, clusterin, \u03b12-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin, and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Additionally, viral amyloid induction led to a dramatic drop in the soluble protein concentration in the CSF. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF and result in soluble protein depletion, thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.", "doi": "10.1021/acschemneuro.4c00636", "pmid": "39510798", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Global Proteomics and Proteogenomics": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2024-11-15T09:02:02.653Z", "modified": "2025-04-07T07:30:58.294Z"}, {"entity": "publication", "iuid": "a3bdea4aa2d845f58b75e41eb55c7da1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a3bdea4aa2d845f58b75e41eb55c7da1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a3bdea4aa2d845f58b75e41eb55c7da1"}}, "title": "Increased CSF DOPA Decarboxylase Correlates with Lower DaT-SPECT Binding: Analyses in Biopark and PPMI Cohorts.", "authors": [{"family": "Khosousi", "given": "Shervin", "initials": "S"}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Appleton", "given": "Ellen", "initials": "E"}, {"family": "Paslawski", "given": "Wojciech", "initials": "W", "orcid": "0000-0003-2141-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce039c7e5e774d66a8c0331a3c990ccc.json"}}, {"family": "Ta", "given": "Michael", "initials": "M", "orcid": "0000-0001-6148-3841", "researcher": {"href": "https://publications.scilifelab.se/researcher/30644bee13c940409e1bca9a26bcfece.json"}}, {"family": "Nalls", "given": "Michael", "initials": "M"}, {"family": "Singleton", "given": "Andrew B", "initials": "AB"}, {"family": "Iwaki", "given": "Hirotaka", "initials": "H", "orcid": "0000-0002-8982-7885", "researcher": {"href": "https://publications.scilifelab.se/researcher/a35d8047c1ef434ab616cc370979d7e8.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "Mov Disord", "issn": "1531-8257", "volume": "39", "issue": "10", "pages": "1881-1885", "issn-l": null}, "abstract": "Recent studies identified increased cerebrospinal fluid (CSF) DOPA decarboxylase (DDC) as a promising biomarker for parkinsonian disorders, suggesting a compensation to dying dopaminergic neurons. A correlation with 123I-FP-CIT-SPECT (DaT-SPECT) imaging could shed light on this link.\n\nThe objective is to assess the relationship between CSF DDC levels and DaT-SPECT binding values.\n\nA total of 51 and 72 Parkinson's disease (PD) subjects with available DaT-SPECT and CSF DDC levels were selected from the PPMI and Biopark cohorts, respectively. DDC levels were analyzed using proximity extension assay and correlated with DaT-SPECT striatal binding ratios (SBR). All analyses were corrected for age and sex.\n\nCSF DDC levels in PD patients correlated negatively with DaT-SPECT SBR in both putamen and caudate nucleus. Additionally, SBR decreased with increased DDC levels over time in PD patients.\n\nCSF DDC levels negatively correlate with DaT-SPECT SBR in levodopa-treated PD. \u00a9 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.", "doi": "10.1002/mds.29835", "pmid": "38798037", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1991855"}, {"db": "pmc", "key": "PMC11490393"}], "notes": [], "created": "2024-11-14T23:01:21.209Z", "modified": "2024-11-14T23:01:24.058Z"}, {"entity": "publication", "iuid": "d82774b91b3543f98a71d6c065a62093", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d82774b91b3543f98a71d6c065a62093.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d82774b91b3543f98a71d6c065a62093"}}, "title": "Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice.", "authors": [{"family": "Mantas", "given": "Ioannis", "initials": "I", "orcid": "0000-0001-6288-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/025776ae147144dab1e2f10a5761b9ed.json"}}, {"family": "Flais", "given": "Ivana", "initials": "I"}, {"family": "Masarapu", "given": "Yuvarani", "initials": "Y", "orcid": "0000-0002-3267-2085", "researcher": {"href": "https://publications.scilifelab.se/researcher/055fa17f6cdd490e87182c94c847c440.json"}}, {"family": "Ionescu", "given": "Tudor", "initials": "T"}, {"family": "Frapard", "given": "Sol\u00e8ne", "initials": "S", "orcid": "0000-0002-2649-7225", "researcher": {"href": "https://publications.scilifelab.se/researcher/a336a6a31fae4766afbb5e376a4a12a3.json"}}, {"family": "Jung", "given": "Felix", "initials": "F"}, {"family": "Le Merre", "given": "Pierre", "initials": "P", "orcid": "0000-0003-4205-7411", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba592e9aa93b433cb85ff11a786b0a71.json"}}, {"family": "Saarinen", "given": "Marcus", "initials": "M"}, {"family": "Tiklova", "given": "Katarina", "initials": "K"}, {"family": "Salmani", "given": "Behzad Yaghmaeian", "initials": "BY", "orcid": "0000-0002-4221-6243", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb9b5976d0b34622aff0e9a564b3ae54.json"}}, {"family": "Gillberg", "given": "Linda", "initials": "L"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X", "orcid": "0000-0002-9461-8682", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f307c88103d43b1b0b893fa59a8e828.json"}}, {"family": "Chergui", "given": "Karima", "initials": "K"}, {"family": "Carl\u00e9n", "given": "Marie", "initials": "M", "orcid": "0000-0003-1658-1631", "researcher": {"href": "https://publications.scilifelab.se/researcher/88931dd9e39c48e2820b89080c3945ad.json"}}, {"family": "Giacomello", "given": "Stefania", "initials": "S", "orcid": "0000-0003-0738-1574", "researcher": {"href": "https://publications.scilifelab.se/researcher/8499e792cc394c42b4240ef5fb3fd06c.json"}}, {"family": "Hengerer", "given": "Bastian", "initials": "B", "orcid": "0000-0002-7811-9795", "researcher": {"href": "https://publications.scilifelab.se/researcher/2adf2c1fe0954f018f91ebce7d06d945.json"}}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2024-09-18", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "8176", "issn-l": "2041-1723"}, "abstract": "The Claustrum/dorsal endopiriform cortex complex (CLA) is an enigmatic brain region with extensive glutamatergic projections to multiple cortical areas. The transcription factor Nurr1 is highly expressed in the CLA, but its role in this region is not understood. By using conditional gene-targeted mice, we show that Nurr1 is a crucial regulator of CLA neuron identity. Although CLA neurons remain intact in the absence of Nurr1, the distinctive gene expression pattern in the CLA is abolished. CLA has been hypothesized to control hallucinations, but little is known of how the CLA responds to hallucinogens. After the deletion of Nurr1 in the CLA, both hallucinogen receptor expression and signaling are lost. Furthermore, functional ultrasound and Neuropixel electrophysiological recordings revealed that the hallucinogenic-receptor agonists' effects on functional connectivity between prefrontal and sensorimotor cortices are altered in Nurr1-ablated mice. Our findings suggest that Nurr1-targeted strategies provide additional avenues for functional studies of the CLA.", "doi": "10.1038/s41467-024-52429-9", "pmid": "39289358", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Other": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11408527"}, {"db": "pii", "key": "10.1038/s41467-024-52429-9"}], "notes": [], "created": "2024-10-31T12:38:39.729Z", "modified": "2024-10-31T12:38:39.977Z"}, {"entity": "publication", "iuid": "4e32b1a69fb9494d8f947125c273d792", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4e32b1a69fb9494d8f947125c273d792.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4e32b1a69fb9494d8f947125c273d792"}}, "title": "AlphaFold accelerated discovery of psychotropic agonists targeting the trace amine-associated receptor 1.", "authors": [{"family": "D\u00edaz-Holgu\u00edn", "given": "Alejandro", "initials": "A", "orcid": "0000-0002-3449-5086", "researcher": {"href": "https://publications.scilifelab.se/researcher/335c8b7a0b6043fc984a1d21b77f721b.json"}}, {"family": "Saarinen", "given": "Marcus", "initials": "M"}, {"family": "Vo", "given": "Duc Duy", "initials": "DD"}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Branzell", "given": "Niclas", "initials": "N"}, {"family": "Cabeza de Vaca", "given": "Israel", "initials": "I", "orcid": "0000-0002-6208-1091", "researcher": {"href": "https://publications.scilifelab.se/researcher/65628edbdaa448b8ab37d5eb4e100aee.json"}}, {"family": "Hu", "given": "Huabin", "initials": "H"}, {"family": "Mitjavila-Dom\u00e8nech", "given": "N\u00faria", "initials": "N"}, {"family": "Lindqvist", "given": "Annika", "initials": "A", "orcid": "0009-0003-2587-8434", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6e7610970e64dcba383e49b60df4f50.json"}}, {"family": "Baranczewski", "given": "Pawel", "initials": "P", "orcid": "0000-0001-5772-6791", "researcher": {"href": "https://publications.scilifelab.se/researcher/47f7af2466c14275a42aad4a431b2dcb.json"}}, {"family": "Millan", "given": "Mark J", "initials": "MJ"}, {"family": "Yang", "given": "Yunting", "initials": "Y", "orcid": "0000-0001-5700-1547", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f8478fd3a4d4a2c8280843835b543d9.json"}}, {"family": "Carlsson", "given": "Jens", "initials": "J", "orcid": "0000-0003-4623-2977", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7d91087358e46e38bb1b7110dc0b214.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2024-08-09", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "10", "issue": "32", "pages": "eadn1524", "issn-l": "2375-2548"}, "abstract": "Artificial intelligence is revolutionizing protein structure prediction, providing unprecedented opportunities for drug design. To assess the potential impact on ligand discovery, we compared virtual screens using protein structures generated by the AlphaFold machine learning method and traditional homology modeling. More than 16 million compounds were docked to models of the trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor of unknown structure and target for treating neuropsychiatric disorders. Sets of 30 and 32 highly ranked compounds from the AlphaFold and homology model screens, respectively, were experimentally evaluated. Of these, 25 were TAAR1 agonists with potencies ranging from 12 to 0.03 \u03bcM. The AlphaFold screen yielded a more than twofold higher hit rate (60%) than the homology model and discovered the most potent agonists. A TAAR1 agonist with a promising selectivity profile and drug-like properties showed physiological and antipsychotic-like effects in wild-type but not in TAAR1 knockout mice. These results demonstrate that AlphaFold structures can accelerate drug discovery.", "doi": "10.1126/sciadv.adn1524", "pmid": "39110804", "labels": {"Chemical Biology Consortium Sweden": "Service", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11305387"}], "notes": [], "created": "2024-08-16T12:19:56.237Z", "modified": "2025-10-17T13:05:07.343Z"}, {"entity": "publication", "iuid": "a5fc0e258a3b4cb69099d64dacf0cadc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5fc0e258a3b4cb69099d64dacf0cadc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5fc0e258a3b4cb69099d64dacf0cadc"}}, "title": "DOPA-decarboxylase is elevated in CSF, but not plasma, in prodromal and de novo Parkinson's disease.", "authors": [{"family": "Appleton", "given": "Ellen", "initials": "E"}, {"family": "Khosousi", "given": "Shervin", "initials": "S"}, {"family": "Ta", "given": "Michael", "initials": "M"}, {"family": "Nalls", "given": "Michael", "initials": "M"}, {"family": "Singleton", "given": "Andrew B", "initials": "AB"}, {"family": "Sturchio", "given": "Andrea", "initials": "A"}, {"family": "Markaki", "given": "Ioanna", "initials": "I"}, {"family": "Paslawski", "given": "Wojciech", "initials": "W"}, {"family": "Iwaki", "given": "Hirotaka", "initials": "H"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "letter", "published": "2024-06-11", "journal": {"title": "Transl Neurodegener", "issn": "2047-9158", "volume": "13", "issue": "1", "pages": "31", "issn-l": null}, "abstract": null, "doi": "10.1186/s40035-024-00421-0", "pmid": "38863007", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11165760"}, {"db": "pii", "key": "10.1186/s40035-024-00421-0"}], "notes": [], "created": "2024-11-05T17:35:33.298Z", "modified": "2024-11-05T17:35:33.352Z"}, {"entity": "publication", "iuid": "4963e447551c4e0c8c3cb79a1700968b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4963e447551c4e0c8c3cb79a1700968b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4963e447551c4e0c8c3cb79a1700968b"}}, "title": "PARKIN is not required to sustain OXPHOS function in adult mammalian tissues.", "authors": [{"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.json"}}, {"family": "Gerlach", "given": "Jule", "initials": "J"}, {"family": "Choi", "given": "Hae-Na", "initials": "H"}, {"family": "Rigoni", "given": "Giovanni", "initials": "G"}, {"family": "Barbaro", "given": "Michela", "initials": "M", "orcid": "0000-0002-7598-9330", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa6b9b246e0d4187be04071f5a53574f.json"}}, {"family": "Oscarson", "given": "Mikael", "initials": "M"}, {"family": "Lee", "given": "Seungmin", "initials": "S"}, {"family": "Tiklova", "given": "Katarina", "initials": "K"}, {"family": "Ringn\u00e9r", "given": "Markus", "initials": "M", "orcid": "0000-0001-5469-8940", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0308e6d9c534033b431d2552cfe2af6.json"}}, {"family": "Koolmeister", "given": "Camilla", "initials": "C"}, {"family": "Wibom", "given": "Rolf", "initials": "R"}, {"family": "Riggare", "given": "Sara", "initials": "S", "orcid": "0000-0002-2256-7310", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa5451b97aa140e0b1e9355be9fd9343.json"}}, {"family": "Nennesmo", "given": "Inger", "initials": "I"}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Motori", "given": "Elisa", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "N"}], "type": "journal article", "published": "2024-04-29", "journal": {"title": "NPJ Parkinsons Dis", "issn": "2373-8057", "issn-l": null, "volume": "10", "issue": "1", "pages": "93"}, "abstract": "Loss-of-function variants in the PRKN gene encoding the ubiquitin E3 ligase PARKIN cause autosomal recessive early-onset Parkinson's disease (PD). Extensive in vitro and in vivo studies have reported that PARKIN is involved in multiple pathways of mitochondrial quality control, including mitochondrial degradation and biogenesis. However, these findings are surrounded by substantial controversy due to conflicting experimental data. In addition, the existing PARKIN-deficient mouse models have failed to faithfully recapitulate PD phenotypes. Therefore, we have investigated the mitochondrial role of PARKIN during ageing and in response to stress by employing a series of conditional Parkin knockout mice. We report that PARKIN loss does not affect oxidative phosphorylation (OXPHOS) capacity and mitochondrial DNA (mtDNA) levels in the brain, heart, and skeletal muscle of aged mice. We also demonstrate that PARKIN deficiency does not exacerbate the brain defects and the pro-inflammatory phenotype observed in mice carrying high levels of mtDNA mutations. To rule out compensatory mechanisms activated during embryonic development of Parkin-deficient mice, we generated a mouse model where loss of PARKIN was induced in adult dopaminergic (DA) neurons. Surprisingly, also these mice did not show motor impairment or neurodegeneration, and no major transcriptional changes were found in isolated midbrain DA neurons. Finally, we report a patient with compound heterozygous PRKN pathogenic variants that lacks PARKIN and has developed PD. The PARKIN deficiency did not impair OXPHOS activities or induce mitochondrial pathology in skeletal muscle from the patient. Altogether, our results argue that PARKIN is dispensable for OXPHOS function in adult mammalian tissues.", "doi": "10.1038/s41531-024-00707-0", "pmid": "38684669", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11058849"}, {"db": "pii", "key": "10.1038/s41531-024-00707-0"}], "notes": [], "created": "2024-11-12T13:26:45.032Z", "modified": "2024-11-14T20:13:50.645Z"}, {"entity": "publication", "iuid": "b940b2fe317c4dc4a3d7456dcd8cf7e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b940b2fe317c4dc4a3d7456dcd8cf7e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b940b2fe317c4dc4a3d7456dcd8cf7e8"}}, "title": "Secretome Analyses Identify FKBP4 as a GBA1-Associated Protein in CSF and iPS Cells from Parkinson's Disease Patients with GBA1 Mutations.", "authors": [{"family": "Kojima", "given": "Rika", "initials": "R", "orcid": "0000-0002-2745-960X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f78bd62e8f3448cf995c39f0030451ad.json"}}, {"family": "Paslawski", "given": "Wojciech", "initials": "W", "orcid": "0000-0003-2141-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce039c7e5e774d66a8c0331a3c990ccc.json"}}, {"family": "Lyu", "given": "Guochang", "initials": "G"}, {"family": "Arenas", "given": "Ernest", "initials": "E", "orcid": "0000-0003-0197-6577", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3bb18ad1c4b4dae99b60ab0ae13e36a.json"}}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2024-01-04", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "1", "issn-l": null}, "abstract": "Mutations in the GBA1 gene increase the risk of developing Parkinson's disease (PD). However, most carriers of GBA1 mutations do not develop PD throughout their lives. The mechanisms of how GBA1 mutations contribute to PD pathogenesis remain unclear. Cerebrospinal fluid (CSF) is used for detecting pathological conditions of diseases, providing insights into the molecular mechanisms underlying neurodegenerative disorders. In this study, we utilized the proximity extension assay to examine the levels of metabolism-linked protein in the CSF from 17 PD patients carrying GBA1 mutations (GBA1-PD) and 17 idiopathic PD (iPD). The analysis of CSF secretome in GBA1-PD identified 11 significantly altered proteins, namely FKBP4, THOP1, GLRX, TXNDC5, GAL, SEMA3F, CRKL, APLP1, LRP11, CD164, and NPTXR. To investigate GBA1-associated CSF changes attributed to specific neuronal subtypes responsible for PD, we analyzed the cell culture supernatant from GBA1-PD-induced pluripotent stem cell (iPSC)-derived midbrain dopaminergic (mDA) neurons. The secretome analysis of GBA1-PD iPSC-derived mDA neurons revealed that five differently regulated proteins overlapped with those identified in the CSF analysis: FKBP4, THOP1, GLRX, GAL, and CRKL. Reduced intracellular level of the top hit, FKPB4, was confirmed via Western Blot. In conclusion, our findings identify significantly altered CSF GBA1-PD-associated proteins with FKPB4 being firmly attributed to mDA neurons.", "doi": "10.3390/ijms25010683", "pmid": "38203854", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10779269"}, {"db": "pii", "key": "ijms25010683"}], "notes": [], "created": "2024-11-05T17:45:27.948Z", "modified": "2024-11-14T23:12:26.939Z"}, {"entity": "publication", "iuid": "4555fc7b277b4c99b53435715afcc6a2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4555fc7b277b4c99b53435715afcc6a2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4555fc7b277b4c99b53435715afcc6a2"}}, "title": "Prosaposin maintains lipid homeostasis in dopamine neurons and counteracts experimental parkinsonism in rodents.", "authors": [{"family": "He", "given": "Yachao", "initials": "Y", "orcid": "0000-0002-0241-2901", "researcher": {"href": "https://publications.scilifelab.se/researcher/80733d0ca6fa45d7b9133ac217de6e18.json"}}, {"family": "Kaya", "given": "Ibrahim", "initials": "I", "orcid": "0000-0003-3345-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/99a00a900df8419f96fafa97344e56ea.json"}}, {"family": "Shariatgorji", "given": "Reza", "initials": "R", "orcid": "0000-0001-9484-0921", "researcher": {"href": "https://publications.scilifelab.se/researcher/7762e9f6779c4780a4077c557eb7a3b6.json"}}, {"family": "Lundkvist", "given": "Johan", "initials": "J"}, {"family": "Wahlberg", "given": "Lars U", "initials": "LU"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Mamula", "given": "Dejan", "initials": "D"}, {"family": "Kehr", "given": "Jan", "initials": "J"}, {"family": "Zareba-Paslawska", "given": "Justyna", "initials": "J", "orcid": "0000-0001-6193-5908", "researcher": {"href": "https://publications.scilifelab.se/researcher/632ee1b0b103420ea8c98cefb18244a4.json"}}, {"family": "Biverst\u00e5l", "given": "Henrik", "initials": "H", "orcid": "0000-0002-2097-7658", "researcher": {"href": "https://publications.scilifelab.se/researcher/e599409acaaf45b880fc45a65e9bd664.json"}}, {"family": "Chergui", "given": "Karima", "initials": "K"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Andren", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2023-09-19", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "5804"}, "abstract": "Prosaposin (PSAP) modulates glycosphingolipid metabolism and variants have been linked to Parkinson's disease (PD). Here, we find altered PSAP levels in the plasma, CSF and post-mortem brain of PD patients. Altered plasma and CSF PSAP levels correlate with PD-related motor impairments. Dopaminergic PSAP-deficient (cPSAPDAT) mice display hypolocomotion and depression/anxiety-like symptoms with mildly impaired dopaminergic neurotransmission, while serotonergic PSAP-deficient (cPSAPSERT) mice behave normally. Spatial lipidomics revealed an accumulation of highly unsaturated and shortened lipids and reduction of sphingolipids throughout the brains of cPSAPDAT mice. The overexpression of \u03b1-synuclein via AAV lead to more severe dopaminergic degeneration and higher p-Ser129 \u03b1-synuclein levels in cPSAPDAT mice compared to WT mice. Overexpression of PSAP via AAV and encapsulated cell biodelivery protected against 6-OHDA and \u03b1-synuclein toxicity in wild-type rodents. Thus, these findings suggest PSAP may maintain dopaminergic lipid homeostasis, which is dysregulated in PD, and counteract experimental parkinsonism.", "doi": "10.1038/s41467-023-41539-5", "pmid": "37726325", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10509278"}, {"db": "pii", "key": "10.1038/s41467-023-41539-5"}], "notes": [], "created": "2023-11-30T10:50:10.413Z", "modified": "2024-02-09T14:28:28.286Z"}, {"entity": "publication", "iuid": "f2f3f9e8369047b7b94cca2697cc6442", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f2f3f9e8369047b7b94cca2697cc6442.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f2f3f9e8369047b7b94cca2697cc6442"}}, "title": "Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson's disease.", "authors": [{"family": "Paslawski", "given": "Wojciech", "initials": "W"}, {"family": "Khosousi", "given": "Shervin", "initials": "S"}, {"family": "Hertz", "given": "Ellen", "initials": "E"}, {"family": "Markaki", "given": "Ioanna", "initials": "I"}, {"family": "Boxer", "given": "Adam", "initials": "A"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}], "type": "journal article", "published": "2023-09-04", "journal": {"title": "Transl Neurodegener", "issn": "2047-9158", "volume": "12", "issue": "1", "pages": "42", "issn-l": null}, "abstract": "There is a need for biomarkers to support an accurate diagnosis of Parkinson's disease (PD). Cerebrospinal fluid (CSF) has been a successful biofluid for finding neurodegenerative biomarkers, and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies. Using a large-scale multiplex proximity extension assay (PEA) approach, we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders (APD).\n\nCSF from patients with PD, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), multiple system atrophy and controls, were analysed with Olink PEA panels. Three cohorts were used in this study, comprising 192, 88 and 36 cases, respectively. All samples were run on the Cardiovascular II, Oncology II and Metabolism PEA panels.\n\nOur analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts, respectively, compared to controls. Among them, 6 proteins were changed in both cohorts. Midkine (MK) was increased in PD with the strongest effect size and results were validated with ELISA. Another most increased protein in PD, DOPA decarboxylase (DDC), which catalyses the decarboxylation of DOPA (L-3,4-dihydroxyphenylalanine) to dopamine, was strongly correlated with dopaminergic treatment. Moreover, Kallikrein 10 was specifically changed in APD compared with both PD and controls, but unchanged between PD and controls. Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.\n\nUsing the large-scale PEA approach, we have identified potential novel PD diagnostic biomarkers, most notably MK and DDC, in the CSF of PD patients.", "doi": "10.1186/s40035-023-00374-w", "pmid": "37667404", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10476347"}, {"db": "pii", "key": "10.1186/s40035-023-00374-w"}], "notes": [], "created": "2023-09-05T11:23:34.771Z", "modified": "2023-10-03T17:29:22.435Z"}, {"entity": "publication", "iuid": "a9801178dbec4953a293f9964bcbc340", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a9801178dbec4953a293f9964bcbc340.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a9801178dbec4953a293f9964bcbc340"}}, "title": "Spatial lipidomics reveals brain region-specific changes of sulfatides in an experimental MPTP Parkinson's disease primate model.", "authors": [{"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Lupt\u00e1kov\u00e1", "given": "Dominika", "initials": "D", "orcid": "0000-0002-3691-2584", "researcher": {"href": "https://publications.scilifelab.se/researcher/d87af7268aa8418db2b32c560c291d57.json"}}, {"family": "He", "given": "Yachao", "initials": "Y", "orcid": "0000-0002-0241-2901", "researcher": {"href": "https://publications.scilifelab.se/researcher/80733d0ca6fa45d7b9133ac217de6e18.json"}}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1477-7756", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae610b7669754328a119654fdfcd6af4.json"}}, {"family": "Bj\u00e4rterot", "given": "Patrik", "initials": "P", "orcid": "0000-0002-4350-5530", "researcher": {"href": "https://publications.scilifelab.se/researcher/bea1b606a9e149c8846bf0e155c80c6c.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications.scilifelab.se/researcher/c33e3029113549ea96e60c7952e5a19a.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2023-07-26", "journal": {"title": "NPJ Parkinsons Dis", "issn": "2373-8057", "volume": "9", "issue": "1", "pages": "118", "issn-l": null}, "abstract": "Metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to the neurotoxin MPP+ in the brain causes permanent Parkinson's disease-like symptoms by destroying dopaminergic neurons in the pars compacta of the substantia nigra in humans and non-human primates. However, the complete molecular pathology underlying MPTP-induced parkinsonism remains poorly understood. We used dual polarity matrix-assisted laser desorption/ionization mass spectrometry imaging to thoroughly image numerous glycerophospholipids and sphingolipids in coronal brain tissue sections of MPTP-lesioned and control non-human primate brains (Macaca mulatta). The results revealed specific distributions of several sulfatide lipid molecules based on chain-length, number of double bonds, and importantly, hydroxylation stage. More specifically, certain long-chain hydroxylated sulfatides with polyunsaturated chains in the molecular structure were depleted within motor-related brain regions in the MPTP-lesioned animals, e.g., external and internal segments of globus pallidus and substantia nigra pars reticulata. In contrast, certain long-chain non-hydroxylated sulfatides were found to be elevated within the same brain regions. These findings demonstrate region-specific dysregulation of sulfatide metabolism within the MPTP-lesioned macaque brain. The depletion of long-chain hydroxylated sulfatides in the MPTP-induced pathology indicates oxidative stress and oligodendrocyte/myelin damage within the pathologically relevant brain regions. Hence, the presented findings improve our current understanding of the molecular pathology of MPTP-induced parkinsonism within primate brains, and provide a basis for further research regarding the role of dysregulated sulfatide metabolism in PD.", "doi": "10.1038/s41531-023-00558-1", "pmid": "37495571", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC10372136"}, {"db": "pii", "key": "10.1038/s41531-023-00558-1"}], "notes": [], "created": "2023-11-30T10:15:39.072Z", "modified": "2023-11-30T10:15:39.211Z"}, {"entity": "publication", "iuid": "ae4ff1411a31429f8d1c53a6fc16ed11", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ae4ff1411a31429f8d1c53a6fc16ed11.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ae4ff1411a31429f8d1c53a6fc16ed11"}}, "title": "PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons.", "authors": [{"family": "Toskas", "given": "Konstantinos", "initials": "K", "orcid": "0000-0002-5897-9501", "researcher": {"href": "https://publications.scilifelab.se/researcher/687adc14acf7400eaa552f41eb39807e.json"}}, {"family": "Yaghmaeian-Salmani", "given": "Behzad", "initials": "B", "orcid": "0000-0002-4221-6243", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb9b5976d0b34622aff0e9a564b3ae54.json"}}, {"family": "Skiteva", "given": "Olga", "initials": "O"}, {"family": "Paslawski", "given": "Wojciech", "initials": "W", "orcid": "0000-0003-2141-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce039c7e5e774d66a8c0331a3c990ccc.json"}}, {"family": "Gillberg", "given": "Linda", "initials": "L"}, {"family": "Skara", "given": "Vasiliki", "initials": "V", "orcid": "0000-0002-0017-6116", "researcher": {"href": "https://publications.scilifelab.se/researcher/e412dda73e2e40a380e10775f45fbd66.json"}}, {"family": "Antoniou", "given": "Irene", "initials": "I", "orcid": "0000-0002-3616-9049", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a00a046dece4cae9afa12a5c7caa723.json"}}, {"family": "S\u00f6dersten", "given": "Erik", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Chergui", "given": "Karima", "initials": "K", "orcid": "0000-0001-5702-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/be439b7cafce4d919881a7b0ef7d6340.json"}}, {"family": "Ringn\u00e9r", "given": "Markus", "initials": "M", "orcid": "0000-0001-5469-8940", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0308e6d9c534033b431d2552cfe2af6.json"}}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Holmberg", "given": "Johan", "initials": "J", "orcid": "0000-0002-3018-001X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f84bece88a264d228d3770ca634b4a19.json"}}], "type": "journal article", "published": "2022-08-26", "journal": {"title": "Sci Adv", "issn": "2375-2548", "issn-l": "2375-2548", "volume": "8", "issue": "34", "pages": "eabo1543"}, "abstract": "How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, Eed, in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications. Notably, H3K9me3 was lost at these PRC2 targets before gene activation. Neuronal survival was not compromised; instead, there was a reduction in subtype-specific gene expression and a progressive impairment of dopaminergic and serotonergic neuronal function, leading to behavioral deficits characteristic of Parkinson's disease and anxiety. Single-cell analysis revealed subtype-specific vulnerability to loss of PRC2 repression in dopamine neurons of the substantia nigra. Our study reveals that a PRC2-dependent nonpermissive chromatin state is essential to maintain the subtype identity and function of dopaminergic and serotonergic neurons.", "doi": "10.1126/sciadv.abo1543", "pmid": "36026451", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "NGI Single cell": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9417181"}], "notes": [], "created": "2022-08-30T11:39:49.253Z", "modified": "2024-10-14T11:50:28.807Z"}, {"entity": "publication", "iuid": "aab5be8b28f949029e6e9dafb461eca8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aab5be8b28f949029e6e9dafb461eca8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aab5be8b28f949029e6e9dafb461eca8"}}, "title": "Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA-induced dyskinesia.", "authors": [{"family": "Fridjonsdottir", "given": "Elva", "initials": "E", "orcid": "0000-0002-3779-3556", "researcher": {"href": "https://publications.scilifelab.se/researcher/d39a6e68683d4414bb87a0dc7033a7a4.json"}}, {"family": "Shariatgorji", "given": "Reza", "initials": "R", "orcid": "0000-0001-9484-0921", "researcher": {"href": "https://publications.scilifelab.se/researcher/7762e9f6779c4780a4077c557eb7a3b6.json"}}, {"family": "Nilsson", "given": "Anna", "initials": "A", "orcid": "0000-0002-6183-6931", "researcher": {"href": "https://publications.scilifelab.se/researcher/79c9fe163d31414e8b66aa0834538627.json"}}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T", "orcid": "0000-0002-1477-7756", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae610b7669754328a119654fdfcd6af4.json"}}, {"family": "Odell", "given": "Luke R", "initials": "LR", "orcid": "0000-0001-7658-5103", "researcher": {"href": "https://publications.scilifelab.se/researcher/7653ba79ce9d4e4a80be4b42f516680b.json"}}, {"family": "Schembri", "given": "Luke S", "initials": "LS", "orcid": "0000-0001-5588-1077", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dc760b581324125816ed40eb748104c.json"}}, {"family": "Svenningsson", "given": "Per", "initials": "P", "orcid": "0000-0001-6727-3802", "researcher": {"href": "https://publications.scilifelab.se/researcher/5199496295334771ba3c5621a83a6f43.json"}}, {"family": "Fernagut", "given": "Pierre-Olivier", "initials": "P"}, {"family": "Crossman", "given": "Alan R", "initials": "AR"}, {"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications.scilifelab.se/researcher/c33e3029113549ea96e60c7952e5a19a.json"}}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "issn-l": "2375-2548", "volume": "7", "issue": "2", "pages": null}, "abstract": "l-DOPA treatment for Parkinson's disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA-induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.", "doi": "10.1126/sciadv.abe5948", "pmid": "33523980", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "7/2/eabe5948"}, {"db": "pmc", "key": "PMC7787486"}], "notes": [], "created": "2021-03-26T12:47:07.296Z", "modified": "2024-02-09T14:58:49.154Z"}]}