GRP78 counteracts cell death and protein aggregation caused by mutant huntingtin proteins

Yufeng Jiang; Hailong Lv; Min Liao; Xiaoyuan Xu; Shanshan Huang; Huiping Tan; Ting Peng; Yinong Zhang; He Li

doi:10.1016/j.neulet.2012.03.074

GRP78 counteracts cell death and protein aggregation caused by mutant huntingtin proteins

Neurosci Lett. 2012 May 16;516(2):182-7. doi: 10.1016/j.neulet.2012.03.074. Epub 2012 Apr 2.

Authors

Yufeng Jiang¹, Hailong Lv, Min Liao, Xiaoyuan Xu, Shanshan Huang, Huiping Tan, Ting Peng, Yinong Zhang, He Li

Affiliation

¹ Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

PMID: 22490889
DOI: 10.1016/j.neulet.2012.03.074

Abstract

The ER-localized chaperone glucose-regulated protein (GRP78) protects neurons against excitotoxicity and apoptosis. Here we show that overexpressing GRP78 protects N2a cells against mutant huntingtin proteins, reduces formation of mutant huntingtin aggregates, inhibits caspase-12 activation and blocks cell death. Our data suggest that GRP78 may be a promising therapeutic target for the treatment of Huntington's disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology*
Cell Line
Endoplasmic Reticulum / metabolism
Endoplasmic Reticulum / pathology
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress / physiology
Heat-Shock Proteins / metabolism*
Huntingtin Protein
Huntington Disease / genetics
Huntington Disease / metabolism*
Immunoblotting
Mice
Microscopy, Confocal
Mutant Proteins / metabolism*
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
RNA Interference
Transfection

Substances

Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Hspa5 protein, mouse
Htt protein, mouse
Huntingtin Protein
Mutant Proteins
Nerve Tissue Proteins
Nuclear Proteins