Open AccessA role of Heat Shock Protein 70 in Photoreceptor Cell Death: Potential as a Novel Therapeutic Target in Retinal Degeneration
Author(s) -
Furukawa Ayako,
Koriyama Yoshiki
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12471
Subject(s) - photoreceptor cell , programmed cell death , retinal degeneration , retinitis pigmentosa , microbiology and biotechnology , biology , calpain , hsp70 , retina , heat shock protein , retinal , apoptosis , biochemistry , neuroscience , gene , enzyme
Summary Retinal degenerative diseases ( RD s) such as retinitis pigmentosa ( RP ) are a genetically heterogeneous group of disorders characterized by night blindness and peripheral vision loss, which caused by the dysfunction and death of photoreceptor cells. Although many causative gene mutations have been reported, the final common end stage is photoreceptor cell death. Unfortunately, no effective treatments or therapeutic agents have been discovered. Heat shock protein 70 ( HSP 70) is highly conserved and has antiapoptotic activities. A few reports have shown that HSP 70 plays a role in RD s. Thus, we focused on the role of HSP 70 in photoreceptor cell death. Using the N ‐methyl‐ N ‐nitrosourea ( MNU )‐induced photoreceptor cell death model in mice, we could examine two stages of the novel cell death mechanism; the early stage, including HSP 70 cleavage through protein carbonylation by production of reactive oxygen species, lipid peroxidation and Ca 2+ influx/calpain activation, and the late stage of cathepsin and/or caspase activation. The upregulation of intact HSP 70 expression by its inducer is likely to protect photoreceptor cells. In this review, we focus on the role of HSP 70 and the novel cell death signaling process in RD s. We also describe candidate therapeutic agents for RD s.