Phase Separation and Neurodegenerative Diseases: A Disturbance in the Force

• Published in: Developmental cell Vol. 55; no. 1; pp. 45 - 68
• Main Authors: Zbinden, Aurélie, Pérez-Berlanga, Manuela, De Rossi, Pierre, Polymenidou, Magdalini
• Format: Journal Article
• Language: English
• Published: United States 12.10.2020
• Subjects: DNA-Binding Proteins - metabolism; Humans; Mechanical Phenomena; Neurodegenerative Diseases - metabolism; Protein Aggregates - physiology; Protein Domains - physiology; RNA-Binding Proteins - metabolism; liquid-liquid phase separation; FUS; prion-like; TDP-43; protein aggregation; neurodegeneration; Tau; RNA-binding proteins; α-synuclein; biomolecular condensates
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2020.09.014

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.