Lysophosphatidylcholine binds α-synuclein and prevents its pathological aggregation.
Natl Sci Rev
; 11(6): nwae182, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38962715
ABSTRACT
Accumulation of aggregated α-synuclein (α-syn) in Lewy bodies is the pathological hallmark of Parkinson's disease (PD). Genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism. The role of α-syn's lipid interactions in its function and aggregation is recognized, yet the specific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegeneration remain unclear. Here, we found that α-syn shows a preference for binding to lysophospholipids (LPLs), particularly targeting lysophosphatidylcholine (LPC) without relying on electrostatic interactions. LPC is capable of maintaining α-syn in a compact conformation, significantly reducing its propensity to aggregate both in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs is associated with an increase in α-syn accumulation. Our work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potential connection between lipid metabolic dysfunction and α-syn aggregation in PD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Natl Sci Rev
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China