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Protein Reviews pp 1–12Cite as

Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis

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Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 925))

Abstract

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.

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Acknowledgements

This work was supported by Grants-in-aid 25291028, 15H01566, 15K14480 (to Y.F.) and 15H06588 (to E.T.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflicts of Interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Laboratory for Mechanistic Chemistry of Biomolecules, Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Kohoku, Yokohama, 223-8522, Japan

    Yoshiaki Furukawa & Eiichi Tokuda

Authors
  1. Yoshiaki Furukawa
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  2. Eiichi Tokuda
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Correspondence to Yoshiaki Furukawa .

Editor information

Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, Texas, USA

    M. Zouhair Atassi

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© 2016 Springer International Publishing Switzerland

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Furukawa, Y., Tokuda, E. (2016). Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 925. Springer, Singapore. https://doi.org/10.1007/5584_2016_32

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