Observation of an α-synuclein liquid droplet state and its maturation into Lewy body-like assemblies

• 作者: Maarten C.Hardenberg Tessa Sinnige Sam Casford Samuel T.Dada Chetan Poudel Elizabeth A.Robinson Mlonika Fuxreiter Clemens F.Kaminksi Gabriele S.Kaminski Schierle Ellen A.A.Nollen Christopher M.Dobson Michele Vendruscolo
• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2021,（4）
• 所属期刊栏目: Articles
• 页码范围: 282-294
• 页数: 13页
• 语种: 英文
• DOI: 10.1093/jmcb/mjaa075

摘要

Misfolded α-synuclein is a major component of Lewy bodies,which are a hallmark of Parkinson's disease (PD).A large body of ev-idence shows that α-synuclein can aggregate into amyloid fibrils,but the relationship between α-synuclein self-assembly and Lewy body formation remains unclear.Here,we show,both in vitro and in a Caenorhabditis elegans model of PD,that α-synuclein undergoes liquid-liquid phase separation by forming a liquid droplet state,which converts into an amyloid-rich hydrogel with Lewy-body-like properties.This maturation process towards the amyloid state is delayed in the presence of model synaptic vesicles in vitro.Taken together,these results suggest that the formation of Lewy bodies may be linked to the arrested matura-tion of α-synuclein condensates in the presence of lipids and other cellular components.