Histone Deacetylase Inhibitors Increase Glucocerebrosidase Activity in Gaucher Disease by Modulation of Molecular Chaperones

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 Jan 2

PMID 23277556

Citations 49

Authors

Chunzhang Yang

Shervin Rahimpour

Jie Lu

Karel Pacak

Barbara Ikejiri

Roscoe O Brady

Zhengping Zhuang

Affiliations

Soon will be listed here.

Abstract

Gaucher disease is caused by mutations of the GBA gene that encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA mutations often result in protein misfolding and premature degradation, but usually exert less effect on catalytic activity. In this study, we identified the molecular mechanism by which histone deacetylase inhibitors increase the quantity and activity of GCase. Specifically, these inhibitors limit the deacetylation of heat shock protein 90, resulting in less recognition of the mutant peptide and GCase degradation. These findings provide insight into a possible therapeutic strategy for Gaucher disease and other genetic disorders by modifying molecular chaperone and protein degradation pathways.

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