α-Synuclein V15A Variant in Familial Parkinson's Disease Exhibits a Weaker Lipid-Binding Property.

ABSTRACT:

Background

The α-Synuclein (α-Syn) V15A variant has been found in two Caucasian families with Parkinson's disease (PD). However, the significance of this missense variant remained unclear.

Objective

We sought to elucidate whether V15A could increase aggregation or change phospholipid affinity.

Methods

A sequencing analysis for the SNCA encoding α-Syn from 875 patients with PD and 324 control subjects was performed. Comparing with known pathogenic missense variants of α-Syn, A30P, and A53T, we analyzed the effects of V15A on binding to phospholipid membrane, self-aggregation, and seed-dependent aggregation in cultured cells.

Results

Genetic screening identified SNCA c.44 T>C (p.V15A) from two Japanese PD families. The missense variant V15A was extremely rare in

SUBMITTER: Daida K 

PROVIDER: S-EPMC9796804 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature