The GBA1 D409V mutation exacerbates synuclein pathology to differing extents in two alpha-synuclein models.

ABSTRACT: Heterozygous mutations in the GBA1 gene - encoding lysosomal glucocerebrosidase (GCase) - are the most common genetic risk factors for Parkinson's disease (PD). Experimental evidence suggests a correlation between decreased GCase activity and accumulation of alpha-synuclein (aSyn). To enable a better understanding of the relationship between aSyn and GCase activity, we developed and characterized two mouse models that investigate aSyn pathology in the context of reduced GCase activity. The first model used constitutive overexpression of wild-type human aSyn in the context of the homozygous GCase activity-reducing D409V mutant form of GBA1. Although increased aSyn pathology and grip strength reductions were observed in this model, the nigrostriatal system remained largely intact. The second

SUBMITTER: Polinski NK 

PROVIDER: S-EPMC9150115 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature