Article (Scientific journals)
A new synuclein-transgenic mouse model for early Parkinson's reveals molecular features of preclinical disease
Hendrickx, Diana M.; Garcia, Pierre; Ashrafi, Amer et al.
2020In Molecular Neurobiology, 58, p. 576-602
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Keywords :
Parkinson's disease; transgenic mouse model; alpha-synuclein; pathway analysis; network analysis
Abstract :
[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.
Research center :
- Luxembourg Centre for Systems Biomedicine (LCSB): Biomedical Data Science (Glaab Group)
Disciplines :
Life sciences: Multidisciplinary, general & others
Neurology
Biotechnology
Author, co-author :
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  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
External co-authors :
yes
Language :
English
Title :
A new synuclein-transgenic mouse model for early Parkinson's reveals molecular features of preclinical disease
Publication date :
2020
Journal title :
Molecular Neurobiology
ISSN :
1559-1182
Publisher :
Humana Press, United States
Volume :
58
Pages :
576-602
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
FnR Project :
FNR11651464 - Multi-dimensional Stratification Of Parkinson'S Disease Patients For Personalised Interventions, 2017 (01/07/2018-30/06/2021) - Enrico Glaab
Name of the research project :
FNR11651464 > Enrico Glaab > PD-Strat > Multi-dimensional stratification of Parkinson’s disease patients for personalised interventions > 01/07/2018 > 30/06/2021 > 2018
Funders :
FNR - Fonds National de la Recherche [LU]
Available on ORBilu :
since 26 August 2020

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