{"entity": "journal", "iuid": "fb3358de1f314ea0a707847f629a3a01", "timestamp": "2026-05-19T01:23:20.699Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Neurobiol.%20Dis..json"}, "display": {"href": "https://publications.scilifelab.se/journal/Neurobiol.%20Dis."}}, "title": "Neurobiol. Dis.", "issn": "1095-953X", "issn-l": "0969-9961", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "3c879540016f423ca84894bb30eae1b5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c879540016f423ca84894bb30eae1b5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c879540016f423ca84894bb30eae1b5"}}, "title": "Machine learning based multi-omics analysis reveals key molecular determinants of Parkinson's disease severity.", "authors": [{"family": "Jin", "given": "Han", "initials": "H"}, {"family": "Meng", "given": "Lingqi", "initials": "L"}, {"family": "Yulug", "given": "Burak", "initials": "B"}, {"family": "Altay", "given": "Ozlem", "initials": "O"}, {"family": "Li", "given": "Xiangyu", "initials": "X"}, {"family": "Cankaya", "given": "Seyda", "initials": "S"}, {"family": "Hanoglu", "given": "Lutfu", "initials": "L"}, {"family": "Ji", "given": "Boyu", "initials": "B"}, {"family": "Coskun", "given": "Ebru", "initials": "E"}, {"family": "Idil", "given": "Ezgi", "initials": "E"}, {"family": "Nogaylar", "given": "Rahim", "initials": "R"}, {"family": "Oktem", "given": "Ece Ozdemir", "initials": "EO"}, {"family": "Sayman", "given": "Dila", "initials": "D"}, {"family": "Karaca", "given": "Ramazan", "initials": "R"}, {"family": "Ozsimsek", "given": "Ahmet", "initials": "A"}, {"family": "Shoaie", "given": "Saeed", "initials": "S"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Zhang", "given": "Cheng", "initials": "C"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2026-04-30", "journal": {"title": "Neurobiol. Dis.", "issn": "1095-953X", "volume": "225", "pages": "107424", "issn-l": "0969-9961"}, "abstract": "While single-omics analyses of Parkinson's Disease (PD) have demonstrated their ability in revealing the underlying molecular mechanisms, they often fail to provide a comprehensive view of the complete disease mechanisms. In this study, we leveraged multi-omics data from 64 heterogeneous, well-phenotyped PD patients, generated plasma metabolomics data and Olink proteomics data together with the gut and saliva metagenomics data, and investigated the altered molecular mechanisms and their interactions in association with the severity of motor function disorders in PD patients. Based on our multi-omics approach, we identified a panel of 58 biomarkers comprising one clinical variable, 10 proteins, and 17 metabolites from plasma, 26 gut species, and 4 saliva species for PD severity. These biomarkers exhibited superior predictive performance for assessing PD severity compared to those derived from single-omics datasets. The predictive power of our machine learning models based on these biomarkers was validated using additional multi-omics data from the same group of PD patients after a 3-month follow-up. The contribution of each omics dataset was evaluated by both supervised and unsupervised machine learning approaches, highlighting the importance of plasma metabolomics in disease stratification. Our study unveiled disease-related molecular alterations across multiple omics datasets, offering potential diagnostic and therapeutic insights for PD. Moreover, it underpinned the significance of employing multi-omics analyses when studying complex diseases like PD.", "doi": "10.1016/j.nbd.2026.107424", "pmid": "42069091", "labels": {"NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "S0969-9961(26)00169-5"}], "notes": [], "created": "2026-05-11T11:43:55.203Z", "modified": "2026-05-11T11:43:55.359Z"}, {"entity": "publication", "iuid": "7f5fdc800e8a472da81df4319a16cb3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7f5fdc800e8a472da81df4319a16cb3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f5fdc800e8a472da81df4319a16cb3a"}}, "title": "Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis.", "authors": [{"family": "Daura", "given": "Eduard", "initials": "E"}, {"family": "Tegelberg", "given": "Saara", "initials": "S"}, {"family": "Yoshihara", "given": "Masahito", "initials": "M"}, {"family": "Jackson", "given": "Christopher", "initials": "C"}, {"family": "Simonetti", "given": "Francesca", "initials": "F"}, {"family": "Aksentjeff", "given": "Katri", "initials": "K"}, {"family": "Ezer", "given": "Sini", "initials": "S"}, {"family": "Hakala", "given": "Paula", "initials": "P"}, {"family": "Katayama", "given": "Shintaro", "initials": "S"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Lehesjoki", "given": "Anna-Elina", "initials": "AE"}, {"family": "Joensuu", "given": "Tarja", "initials": "T"}], "type": "journal article", "published": "2021-08-00", "journal": {"title": "Neurobiol. Dis.", "issn": "1095-953X", "volume": "156", "pages": "105418", "issn-l": "0969-9961"}, "abstract": "Cystatin B (CSTB) acts as an inhibitor of cysteine proteases of the cathepsin family and loss-of-function mutations result in human brain diseases with a genotype-phenotype correlation. In the most severe case, CSTB-deficiency disrupts brain development, and yet the molecular basis of this mechanism is missing. Here, we establish CSTB as a regulator of chromatin structure during neural stem cell renewal and differentiation. Murine neural precursor cells (NPCs) undergo transient proteolytic cleavage of the N-terminal histone H3 tail by cathepsins B and L upon induction of differentiation into neurons and glia. In contrast, CSTB-deficiency triggers premature H3 tail cleavage in undifferentiated self-renewing NPCs and sustained H3 tail proteolysis in differentiating neural cells. This leads to significant transcriptional changes in NPCs, particularly of nuclear-encoded mitochondrial genes. In turn, these transcriptional alterations impair the enhanced mitochondrial respiration that is induced upon neural stem cell differentiation. Collectively, our findings reveal the basis of epigenetic regulation in the molecular pathogenesis of CSTB deficiency.", "doi": "10.1016/j.nbd.2021.105418", "pmid": "34102276", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0969-9961(21)00167-4"}], "notes": [], "created": "2022-11-09T15:45:26.998Z", "modified": "2024-01-16T13:48:39.027Z"}, {"entity": "publication", "iuid": "7a1f534e1da2463ea333f1d2835a0499", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a1f534e1da2463ea333f1d2835a0499.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a1f534e1da2463ea333f1d2835a0499"}}, "title": "Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy.", "authors": [{"family": "Hulme", "given": "Heather", "initials": "H", "orcid": "0000-0002-2987-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/232094e6f2fc49209ba0ad11b65a1421.json"}}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Gunnarsdottir", "given": "Halla", "initials": "H"}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Wadensten", "given": "Henrik", "initials": "H"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Bezard", "given": "Erwan", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"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": "2020-04-00", "journal": {"title": "Neurobiol. Dis.", "issn": "1095-953X", "volume": "137", "issue": null, "pages": "104738", "issn-l": "0969-9961"}, "abstract": "Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.", "doi": "10.1016/j.nbd.2020.104738", "pmid": "31927144", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "S0969-9961(20)30013-9"}], "notes": [], "created": "2020-01-24T09:26:04.976Z", "modified": "2021-12-03T11:53:06.743Z"}, {"entity": "publication", "iuid": "1a1d372b9e16494cbd68b5793f731edf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1a1d372b9e16494cbd68b5793f731edf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1a1d372b9e16494cbd68b5793f731edf"}}, "title": "Transcriptomes of Dravet syndrome iPSC derived GABAergic cells reveal dysregulated pathways for chromatin remodeling and neurodevelopment.", "authors": [{"family": "Schuster", "given": "Jens", "initials": "J", "orcid": "0000-0002-4383-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/a194d037b21c47a2926b082e9e79de31.json"}}, {"family": "Laan", "given": "Loora", "initials": "L"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Jin", "given": "Zhe", "initials": "Z"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Korol", "given": "Sergiy", "initials": "S"}, {"family": "Noraddin", "given": "Feria Hikmet", "initials": "FH"}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Birnir", "given": "Bryndis", "initials": "B"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"volume": "132", "issn": "1095-953X", "issue": null, "pages": "104583", "title": "Neurobiol. Dis.", "issn-l": "0969-9961"}, "abstract": "Dravet syndrome (DS) is an early onset refractory epilepsy typically caused by de novo heterozygous variants in SCN1A encoding the \u03b1-subunit of the neuronal sodium channel Na v1.1. The syndrome is characterized by age-related progression of seizures, cognitive decline and movement disorders. We hypothesized that the distinct neurodevelopmental features in DS are caused by the disruption of molecular pathways in Nav1.1 haploinsufficient cells resulting in perturbed neural differentiation and maturation. Here, we established DS-patient and control induced pluripotent stem cell derived neural progenitor cells (iPSC NPC) and GABAergic inter-neuronal (iPSC GABA) cells. The DS-patient iPSC GABA cells showed a shift in sodium current activation and a perturbed response to induced oxidative stress. Transcriptome analysis revealed specific dysregulations of genes for chromatin structure, mitotic progression, neural plasticity and excitability in DS-patient iPSC NPCs and DS-patient iPSC GABA cells versus controls. The transcription factors FOXM1 and E2F1, positive regulators of the disrupted pathways for histone modification and cell cycle regulation, were markedly up-regulated in DS-iPSC GABA lines. Our study highlights transcriptional changes and disrupted pathways of chromatin remodeling in Nav1.1 haploinsufficient GABAergic cells, providing a molecular framework that overlaps with that of neurodevelopmental disorders and other epilepsies.", "doi": "10.1016/j.nbd.2019.104583", "pmid": "31445158", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0969-9961(19)30251-7"}], "notes": [], "created": "2019-11-20T15:33:02.190Z", "modified": "2024-01-16T13:48:43.380Z"}, {"entity": "publication", "iuid": "e196eff556fd47aa9db69794a88a5c31", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e196eff556fd47aa9db69794a88a5c31.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e196eff556fd47aa9db69794a88a5c31"}}, "title": "Reactive astrocytes and Wnt/\u03b2-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.", "authors": [{"family": "L'Episcopo", "given": "F", "initials": "F"}, {"family": "Tirolo", "given": "C", "initials": "C"}, {"family": "Testa", "given": "N", "initials": "N"}, {"family": "Caniglia", "given": "S", "initials": "S"}, {"family": "Morale", "given": "M C", "initials": "MC"}, {"family": "Cossetti", "given": "C", "initials": "C"}, {"family": "D'Adamo", "given": "P", "initials": "P"}, {"family": "Zardini", "given": "E", "initials": "E"}, {"family": "Andreoni", "given": "L", "initials": "L"}, {"family": "Ihekwaba", "given": "A E C", "initials": "AE"}, {"family": "Serra", "given": "P A", "initials": "PA"}, {"family": "Franciotta", "given": "D", "initials": "D"}, {"family": "Martino", "given": "G", "initials": "G"}, {"family": "Pluchino", "given": "S", "initials": "S"}, {"family": "Marchetti", "given": "B", "initials": "B"}], "type": "journal article", "published": "2011-02-00", "journal": {"volume": "41", "issn": "1095-953X", "issue": "2", "pages": "508-527", "title": "Neurobiol. Dis.", "issn-l": "0969-9961"}, "abstract": "Emerging evidence points to reactive glia as a pivotal factor in Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of basal ganglia injury, but whether astrocytes and microglia activation may exacerbate dopaminergic (DAergic) neuron demise and/or contribute to DAergic repair is presently the subject of much debate. Here, we have correlated the loss and recovery of the nigrostriatal DAergic functionality upon acute MPTP exposure with extensive gene expression analysis at the level of the ventral midbrain (VM) and striata (Str) and found a major upregulation of pro-inflammatory chemokines and wingless-type MMTV integration site1 (Wnt1), a key transcript involved in midbrain DAergic neurodevelopment. Wnt signaling components (including Frizzled-1 [Fzd-1] and \u03b2-catenin) were dynamically regulated during MPTP-induced DAergic degeneration and reactive glial activation. Activated astrocytes of the ventral midbrain were identified as candidate source of Wnt1 by in situ hybridization and real-time PCR in vitro. Blocking Wnt/Fzd signaling with Dickkopf-1 (Dkk1) counteracted astrocyte-induced neuroprotection against MPP(+) toxicity in primary mesencephalic astrocyte-neuron cultures, in vitro. Moreover, astroglial-derived factors, including Wnt1, promoted neurogenesis and DAergic neurogenesis from adult midbrain stem/neuroprogenitor cells, in vitro. Conversely, lack of Wnt1 transcription in response to MPTP in middle-aged mice and failure of DAergic neurons to recover were reversed by pharmacological activation of Wnt/\u03b2-catenin signaling, in vivo, thus suggesting MPTP-reactive astrocytes in situ and Wnt1 as candidate components of neuroprotective/neurorescue pathways in MPTP-induced nigrostriatal DAergic plasticity.", "doi": "10.1016/j.nbd.2010.10.023", "pmid": "21056667", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "S0969-9961(10)00366-9"}, {"db": "pmc", "key": "PMC3558878"}, {"db": "mid", "key": "EMS51159"}], "notes": [], "created": "2017-05-04T15:03:10.673Z", "modified": "2017-05-30T12:40:16.423Z"}], "created": "2017-05-09T09:12:24.349Z", "modified": "2020-11-27T13:14:01.125Z"}