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α-Synuclein phase separation and amyloid aggregation are modulated by C-terminal truncations.

Shuai HuangXiaoli MoJieyi WangXinyi YeHaijia YuYinghui Liu
Published in: FEBS letters (2022)
The aggregation of α-synuclein (α-Syn) is a key pathological hallmark of Parkinson's disease (PD). α-Syn undergoes liquid-liquid phase separation (LLPS) to drive amyloid aggregation. How the LLPS of α-Syn is regulated remains largely unknown. Here, we discovered that the C-terminal region modulates α-Syn phase separation through electrostatic interactions. The wild-type (WT) and PD disease-related truncated α-Syn can co-exist in the condensates. The truncated α-Syn could dramatically promote WT α-Syn phase separation. Further studies demonstrated that the truncated α-Syn accelerated WT α-Syn turning to amyloid aggregates by modulation of phase separation. Together, our findings disclose the role of the C-terminal domain in the LLPS of α-Syn and pave the path for understanding the mechanism of truncated α-Syn in PD pathology.
Keyphrases
  • wild type
  • transcription factor
  • drug induced