{"entity": "journal", "iuid": "27e2dd9d52d74f179a21ecd7a154c5a9", "timestamp": "2026-07-14T03:43:11.415Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/NPJ%20Parkinsons%20Dis.json"}, "display": {"href": "https://publications.scilifelab.se/journal/NPJ%20Parkinsons%20Dis"}}, "title": "NPJ Parkinsons Dis", "issn": "2373-8057", "issn-l": null, "publications_count": 4, "publications": [{"entity": "publication", "iuid": "2c0506e9af41449186a19fdeda9397c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c0506e9af41449186a19fdeda9397c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c0506e9af41449186a19fdeda9397c7"}}, "title": "Brain-region-specific lipid dysregulation in L-DOPA-induced dyskinesia in a primate model of Parkinson's disease.", "authors": [{"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Bj\u00e4rterot", "given": "Patrik", "initials": "P"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Bezard", "given": "Erwan", "initials": "E"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}], "type": "journal article", "published": "2025-08-23", "journal": {"title": "NPJ Parkinsons Dis", "issn": "2373-8057", "volume": "11", "issue": "1", "pages": "258", "issn-l": null}, "abstract": "L-DOPA-induced dyskinesia (LID) is a significant and treatment-limiting complication in Parkinson's disease (PD) therapy, yet its mechanisms remain poorly understood. We used high-resolution mass spectrometry imaging to map brain-region-specific alterations of glycerophospholipids and sphingolipids in a female macaque model of PD with and without LID following chronic L-DOPA treatment. LID was associated with depletion of antioxidant plasmalogen phosphatidylcholines in the globus pallidus interna, claustrum, and precentral gyrus-regions critical for motor function-and elevations of polyunsaturated fatty acid-containing glycerophospholipids, indicative of increased membrane fluidity. This lipid profile differed from similarly treated non-dyskinetic animals, suggesting lipid composition mediates differential susceptibility to LID. Lipid alterations correlated strongly with dyskinesia severity, dopamine, and L-DOPA concentrations, supporting a mechanistic link between lipid metabolism, neurotransmitter dysregulation, and LID. This comprehensive spatial lipidomic analysis identifies region-specific lipid dysregulation as a novel aspect of LID pathology, highlighting lipid pathways as potential therapeutic targets for mitigating dyskinesia.", "doi": "10.1038/s41531-025-01109-6", "pmid": "40849420", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC12374971"}, {"db": "pii", "key": "10.1038/s41531-025-01109-6"}], "notes": [], "created": "2025-11-21T09:59:50.610Z", "modified": "2025-11-21T09:59:50.625Z"}, {"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": "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": "5638e0d773284335a84a27f885f51078", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5638e0d773284335a84a27f885f51078.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5638e0d773284335a84a27f885f51078"}}, "title": "Basal ganglia neuropeptides show abnormal processing associated with L-DOPA-induced dyskinesia.", "authors": [{"family": "Hulme", "given": "Heather", "initials": "H"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E", "orcid": "0000-0002-3779-3556", "researcher": {"href": "https://publications.scilifelab.se/researcher/d39a6e68683d4414bb87a0dc7033a7a4.json"}}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Li", "given": "Qin", "initials": "Q"}, {"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": "2022-04-13", "journal": {"title": "NPJ Parkinsons Dis", "issn": "2373-8057", "volume": "8", "issue": "1", "pages": "41", "issn-l": null}, "abstract": "L-DOPA administration is the primary treatment for Parkinson's disease (PD) but long-term administration is usually accompanied by hyperkinetic side-effects called L-DOPA-induced dyskinesia (LID). Signaling neuropeptides of the basal ganglia are affected in LID and changes in the expression of neuropeptide precursors have been described, but the final products formed from these precursors have not been well defined and regionally mapped. We therefore used mass spectrometry imaging to visualize and quantify neuropeptides in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposed parkinsonian and LID Macaca mulatta brain samples. We found that dyskinesia severity correlated with the levels of some abnormally processed peptides - notably, des-tyrosine dynorphins, substance P (1-7), and substance P (1-9) - in multiple brain regions. Levels of the active neuropeptides; dynorphin B, dynorphin A (1-8), \u03b1-neoendorphin, substance P (1-11), and neurokinin A, in the globus pallidus and substantia nigra correlated with putaminal levels of L-DOPA. Our results demonstrate that the abundance of selected active neuropeptides is associated with L-DOPA concentrations in the putamen, emphasizing their sensitivity to L-DOPA. Additionally, levels of truncated neuropeptides (which generally exhibit reduced or altered receptor affinity) correlate with dyskinesia severity, particularly for peptides associated with the direct pathway (i.e., dynorphins and tachykinins). The increases in tone of the tachykinin, enkephalin, and dynorphin neuropeptides in LID result in abnormal processing of neuropeptides with different biological activity and may constitute a functional compensatory mechanism for balancing the increased L-DOPA levels across the whole basal ganglia.", "doi": "10.1038/s41531-022-00299-7", "pmid": "35418178", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41531-022-00299-7"}, {"db": "pmc", "key": "PMC9007979"}], "notes": [], "created": "2022-11-16T14:01:50.952Z", "modified": "2022-11-16T14:01:51.004Z"}], "created": "2022-11-16T14:01:50.998Z", "modified": "2022-11-16T14:01:50.998Z"}