Developmental Cell
Volume 55, Issue 1, 12 October 2020, Pages 45-68
Journal home page for Developmental Cell

Review
Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force

https://doi.org/10.1016/j.devcel.2020.09.014Get rights and content
Under an Elsevier user license
open archive

Summary

Protein aggregation is the main hallmark of neurodegenerative diseases. Many proteins found in pathological inclusions are known to undergo liquid-liquid phase separation, a reversible process of molecular self-assembly. Emerging evidence supports the hypothesis that aberrant phase separation behavior may serve as a trigger of protein aggregation in neurodegeneration, and efforts to understand and control the underlying mechanisms are underway. Here, we review similarities and differences among four main proteins, α-synuclein, FUS, tau, and TDP-43, which are found aggregated in different diseases and were independently shown to phase separate. We discuss future directions in the field that will help shed light on the molecular mechanisms of aggregation and neurodegeneration.

Keywords

liquid-liquid phase separation
biomolecular condensates
neurodegeneration
TDP-43
FUS
Tau
α-synuclein
protein aggregation
prion-like
RNA-binding proteins

Cited by (0)

2

These authors contributed equally