Glycine-to-aspartic acid mutation at codon 51 in <i>Snca</i> disrupts the synaptic localisation of α-synuclein and enhances its propensity for synucleinopathy.

ABSTRACT: Point mutations in the SNCA gene, which encodes α-synuclein (αSyn), are a known cause of familial Parkinson's disease. The glycine-51-aspartic acid (G51D) mutation causes early-onset neurodegeneration with complex, wide-spread αSyn pathology. We used CRISPR/Cas9 gene editing to introduce the G51D point mutation into the endogenous rat Snca gene. Our goal was to investigate whether the G51D αSyn mutation gives rise to synucleinopathy and neurodegenerative phenotypes in rats. Co-localisation immunostaining studies with synaptic proteins revealed that αSyn^G51D protein fails to efficiently localise to synapses. Furthermore, biochemical isolation of synaptosomes from rat cortex demonstrated a significant depletion of αSyn in Snca^G51D/+ and Snca

SUBMITTER: West S 

PROVIDER: S-EPMC12198753 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature