Familial mutations modulate α-synuclein interactions with key neuronal membrane lipids.

ABSTRACT: Progressive aggregation of α-synuclein (α-Syn) in the midbrain, hypothalamus and thalamus is linked to Parkinson's disease (PD), one of the fastest growing neurodegenerative diseases in the U.S. Studies of families with PD history revealed several mutations that are responsible for the early-onset (A30P, E46K, A53T) and late-onset (H50Q) forms of PD. A growing body of evidence indicates that phospho-/sphingolipids and cholesterol alter the aggregation properties of wild-type (WT) α-syn. However, the effects of these lipids on the rate of α-syn mutants remain unclear. In the current study, we determined the aggregation rates of A30P, E46K, A53T, H50Q and WT α-syn in the presence of large unilamellar vesicles composed of phosphatidylcholine (PC), sphingomyelin (SM) and cholesterol (Cho)-the

SUBMITTER: Ali A 

PROVIDER: S-EPMC12927006 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature