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Phase separation and neurodegenerative diseases: a disturbance in the force


Zbinden, Aurélie; Pérez-Berlanga, Manuela; De Rossi, Pierre; Polymenidou, Magdalini (2020). Phase separation and neurodegenerative diseases: a disturbance in the force. Developmental Cell, 55(1):45-68.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Quantitative Biomedicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Molecular Biology
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Life Sciences > Developmental Biology
Life Sciences > Cell Biology
Uncontrolled Keywords:Developmental Biology
Language:English
Date:1 October 2020
Deposited On:25 Jan 2021 15:21
Last Modified:26 Jan 2021 21:01
Publisher:Cell Press (Elsevier)
ISSN:1534-5807
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.devcel.2020.09.014

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