Apr 5, 2020

A new synuclein-transgenic mouse model for early Parkinson's reveals molecular features of preclinical disease

BioRxiv : the Preprint Server for Biology
Diana M HendrickxE. Glaab

Abstract

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 -synuclein transgenic mice with a progressive, early PD-like striatum 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 ...Continue Reading

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Mentioned in this Paper

Transcriptional Regulation
Nucleosomes
Transposase
Regulation of Biological Process
Transcription, Genetic
Promoter
Sequence Determinations
Nucleosome Location
Gene Expression
Human Cell Line

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