Reference : A new synuclein-transgenic mouse model for early Parkinson's reveals molecular featur...
Scientific journals : Article
Life sciences : Biotechnology
Life sciences : Multidisciplinary, general & others
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/44128
A new synuclein-transgenic mouse model for early Parkinson's reveals molecular features of preclinical disease
English
Hendrickx, Diana M. []
Garcia, Pierre []
Ashrafi, Amer []
Sciortino, Alessia [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Schmit, Kristopher [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Kollmus, Heike []
Nicot, Nathalie []
Kaoma, Tony []
Vallar, Laurent []
Buttini, Manuel []
Glaab, Enrico mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
In press
Molecular Neurobiology
Humana Press
Yes (verified by ORBilu)
International
0893-7648
1559-1182
United States
[en] Parkinson's disease ; transgenic mouse model ; alpha-synuclein ; pathway analysis ; network analysis
[en] Understanding 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 to investigate 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, 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.
Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Fonds National de la Recherche - FnR
FNR11651464 > Enrico Glaab > PD-Strat > Multi-dimensional stratification of Parkinson’s disease patients for personalised interventions > 01/07/2018 > 30/06/2021 > 2018
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/44128
The hyperlink to the original publication will be provided here once available.
FnR ; FNR11651464 > Enrico Glaab > PD-Strat > Multi-dimensional stratification of Parkinson’s disease patients for personalised interventions > 01/07/2018 > 30/06/2021 > 2018

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