Functional Screening of Parkinson's Disease Susceptibility Genes to Identify Novel Modulators of α-Synuclein Neurotoxicity in Caenorhabditis elegans.

ABSTRACT: Idiopathic Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons during aging. The pathological hallmark of PD is the Lewy body detected in postmortem brain tissue, which is mainly composed of aggregated α-Synuclein (αSyn). However, it is estimated that 90% of PD cases have unknown pathogenetic triggers. Here, we generated a new transgenic Caenorhabditis elegans PD model eraIs1 expressing green fluorescent protein- (GFP-) based reporter of human αSyn in DA neurons, and exhibited a nice readout of the developed αSyn inclusions in DA neurons, leading to their degeneration during aging. Using these animals in a preliminary reverse genetic screening of >100-PD genome-wide association study- (GWAS-) based susceptibility genes, we identified 28

SUBMITTER: Vozdek R 

PROVIDER: S-EPMC9093606 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature