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Heat‐shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS
Author(s) -
Yamashita Hirofumi,
Kawamata Jun,
Okawa Katsuya,
Kanki Rie,
Nakamizo Tomoki,
Hatayama Takumi,
Yamanaka Koji,
Takahashi Ryosuke,
Shimohama Shun
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04534.x
Subject(s) - sod1 , mutant , superoxide dismutase , amyotrophic lateral sclerosis , heat shock protein , chemistry , hsp27 , hsp70 , protein aggregation , mutation , dismutase , microbiology and biotechnology , mutant protein , biochemistry , biology , oxidative stress , gene , pathology , medicine , disease
A dominant mutation in the gene for copper‐zinc superoxide dismutase (SOD1) is the most frequent cause of the inherited form of amyotrophic lateral sclerosis. Mutant SOD1 provokes progressive degeneration of motor neurons by an unidentified acquired toxicity. Exploiting both affinity purification and mass spectrometry, we identified a novel interaction between heat‐shock protein 105 (Hsp105) and mutant SOD1. We detected this interaction both in spinal cord extracts of mutant SOD1 G93A transgenic mice and in cultured neuroblastoma cells. Expression of Hsp105, which is found in mouse motor neurons, was depressed in the spinal cords of SOD1 G93A mice as disease progressed, while levels of expression of two other heat‐shock proteins, Hsp70 and Hsp27, were elevated. Moreover, Hsp105 suppressed the formation of mutant SOD1‐containing aggregates in cultured cells. These results suggest that techniques that raise levels of Hsp105 might be promising tools for alleviation of the mutant SOD1 toxicity.