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Licensed Unlicensed Requires Authentication Published by De Gruyter July 7, 2016

Membrane trafficking and proteolytic activity of γ-secretase in Alzheimer’s disease

  • Kunihiko Kanatsu and Taisuke Tomita ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

γ-Secretase is an intramembrane-cleaving protease that generates various forms of amyloid-β peptides (Aβ) that accumulate in the brains of Alzheimer’s disease (AD) patients. The intracellular trafficking and subcellular localization of γ-secretase are linked to both qualitative and quantitative changes in Aβ production. However, the precise intracellular localization of γ-secretase as well as its detailed regulatory mechanisms have remained elusive. Recent genetic studies on AD provide ample evidence that alteration of the subcellular localization of γ-secretase contributes to the pathogenesis of AD. Here we review our current understanding of the intracellular membrane trafficking of γ-secretase, the association between its localization and proteolytic activity, and the possibility of γ-secretase as a therapeutic target against AD.

Keywords: ; APP; CALM; endocytosis; SORL1

Award Identifier / Grant number: 15H02492

Funding statement: This work was supported in part by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS) (Grant/Award Number: ‘15H02492’), by grants from Takeda Science Foundation, the Cell Science Research Foundation, the Tokyo Biochemical Research Foundation, the Daiichi Sankyo Foundation of Life Science, NAGASE Science Technology Foundation and Ono Medical Research Foundation. K.K. is a research fellow of JSPS.

Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (A) from the Japan Society for the Promotion of Science (JSPS) (Grant/Award Number: ‘15H02492’), by grants from Takeda Science Foundation, the Cell Science Research Foundation, the Tokyo Biochemical Research Foundation, the Daiichi Sankyo Foundation of Life Science, NAGASE Science Technology Foundation and Ono Medical Research Foundation. K.K. is a research fellow of JSPS.

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Received: 2016-2-29
Accepted: 2016-7-4
Published Online: 2016-7-7
Published in Print: 2016-9-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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