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dc.contributor.authorHendrickx, Diana M
dc.contributor.authorGarcia, Pierre
dc.contributor.authorAshrafi, Amer
dc.contributor.authorSciortino, Alessia
dc.contributor.authorSchmit, Kristopher J
dc.contributor.authorKollmus, Heike
dc.contributor.authorNicot, Nathalie
dc.contributor.authorKaoma, Tony
dc.contributor.authorVallar, Laurent
dc.contributor.authorButtini, Manuel
dc.contributor.authorGlaab, Enrico
dc.date.accessioned2020-10-09T11:24:20Z
dc.date.available2020-10-09T11:24:20Z
dc.date.issued2020-09-30
dc.identifier.citationMol Neurobiol. 2020 Sep 30. doi: 10.1007/s12035-020-02085-z. Epub ahead of print.en_US
dc.identifier.pmid32997293
dc.identifier.doi10.1007/s12035-020-02085-z
dc.identifier.urihttp://hdl.handle.net/10033/622505
dc.description.abstractUnderstanding Parkinson's disease (PD), in particular in its earliest phases, is important for diagnosis and treatment. However, human brain samples are collected post-mortem, reflecting mainly end-stage disease. Because brain samples of mouse models can be collected at any stage of the disease process, they are useful in investigating PD progression. Here, we compare ventral midbrain transcriptomics profiles from α-synuclein transgenic mice with a progressive, early PD-like striatal neurodegeneration across different ages using pathway, gene set, and network analysis methods. Our study uncovers statistically significant altered genes across ages and between genotypes with known, suspected, or unknown function in PD pathogenesis and key pathways associated with disease progression. Among those are genotype-dependent alterations associated with synaptic plasticity and neurotransmission, as well as mitochondria-related genes and dysregulation of lipid metabolism. Age-dependent changes were among others observed in neuronal and synaptic activity, calcium homeostasis, and membrane receptor signaling pathways, many of which linked to G-protein coupled receptors. Most importantly, most changes occurred before neurodegeneration was detected in this model, which points to a sequence of gene expression events that may be relevant for disease initiation and progression. It is tempting to speculate that molecular changes similar to those changes observed in our model happen in midbrain dopaminergic neurons before they start to degenerate. In other words, we believe we have uncovered molecular changes that accompany the progression from preclinical to early PD.en_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectDisease-stageen_US
dc.subjectNetwork analysisen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectPathway analysisen_US
dc.subjectTransgenic mouse modelen_US
dc.subjectα-Synucleinen_US
dc.titleA New Synuclein-Transgenic Mouse Model for Early Parkinson's Reveals Molecular Features of Preclinical Disease.en_US
dc.typeArticleen_US
dc.identifier.eissn1559-1182
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalMolecular neurobiologyen_US
refterms.dateFOA2020-10-09T11:24:21Z
dc.source.journaltitleMolecular neurobiology
dc.source.countryUnited States


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