Aggregation of FET proteins as a pathological change in amyotrophic lateral sclerosis

Yoshiaki Furukawa, Eiichi Tokuda

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

3 Citations (Scopus)


Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is characterized by the formation of abnormal inclusions in neurons. While the pathomechanism of ALS remains obscure, a number of proteins have been identified in the inclusion bodies, and the pathological roles of RNA-binding proteins have been increasingly emphasized. Among those, the FET proteins (FUS, EWSR1, TAF15) were recently identified as RNA-binding proteins in pathological inclusions of ALS and other neurodegenerative diseases; moreover, mutations in the genes encoding the FET proteins were found to be associated with familial forms of ALS. FET proteins are normally localized in the nucleus, but the introduction of pathogenic mutations in FET proteins leads to their abnormal redistribution to the cytoplasm, where they form aggregates. While further investigation will be required to understand the intracellular factors controlling the aggregation propensities of FET proteins, they are thought to lose their physiological functions and become toxic through their misfolding/aggregation. Here, we will briefly review recent advances of our understanding of the physiological functions and aggregation behavior of FET proteins in vivo as well as in vitro.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Number of pages12
Publication statusPublished - 2017
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Amyotrophic lateral sclerosis
  • FET family proteins
  • FUS
  • Neurodegenerative diseases
  • Protein aggregation


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