TY - JOUR
T1 - Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration
AU - Kondo, Naohide
AU - Katsuno, Masahisa
AU - Adachi, Hiroaki
AU - Minamiyama, Makoto
AU - Doi, Hideki
AU - Matsumoto, Shinjiro
AU - Miyazaki, Yu
AU - Iida, Madoka
AU - Tohnai, Genki
AU - Nakatsuji, Hideaki
AU - Ishigaki, Shinsuke
AU - Fujioka, Yusuke
AU - Watanabe, Hirohisa
AU - Tanaka, Fumiaki
AU - Nakai, Akira
AU - Sobue, Gen
PY - 2013
Y1 - 2013
N2 - A crucial feature of adult-onset neurodegenerative diseases is accumulation of abnormal protein in specific brain regions, although the mechanism underlying this pathological selectivity remains unclear. Heat shock factor-1 is a transcriptional regulator of heat shock proteins, molecular chaperones that abrogate neurodegeneration by refolding and solubilizing pathogenic proteins. Here we show that heat shock factor-1 expression levels are associated with the accumulation of pathogenic androgen receptor in spinal and bulbar muscular atrophy, a polyglutamine-induced neurodegenerative disease. In heterozygous heat shock factor-1-knockout spinal and bulbar muscular atrophy mice, abnormal androgen receptor accumulates in the cerebral visual cortex, liver and pituitary, which are not affected in their genetically unmodified counterparts. The depletion of heat shock factor-1 also expands the distribution of pathogenic androgen receptor accumulation in other neuronal regions. Furthermore, lentiviral-mediated delivery of heat shock factor-1 into the brain of spinal and bulbar muscular atrophy mice topically suppresses the pathogenic androgen receptor accumulation and neuronal atrophy. These results suggest that heat shock factor-1 influences the pathological lesion selectivity in spinal and bulbar muscular atrophy.
AB - A crucial feature of adult-onset neurodegenerative diseases is accumulation of abnormal protein in specific brain regions, although the mechanism underlying this pathological selectivity remains unclear. Heat shock factor-1 is a transcriptional regulator of heat shock proteins, molecular chaperones that abrogate neurodegeneration by refolding and solubilizing pathogenic proteins. Here we show that heat shock factor-1 expression levels are associated with the accumulation of pathogenic androgen receptor in spinal and bulbar muscular atrophy, a polyglutamine-induced neurodegenerative disease. In heterozygous heat shock factor-1-knockout spinal and bulbar muscular atrophy mice, abnormal androgen receptor accumulates in the cerebral visual cortex, liver and pituitary, which are not affected in their genetically unmodified counterparts. The depletion of heat shock factor-1 also expands the distribution of pathogenic androgen receptor accumulation in other neuronal regions. Furthermore, lentiviral-mediated delivery of heat shock factor-1 into the brain of spinal and bulbar muscular atrophy mice topically suppresses the pathogenic androgen receptor accumulation and neuronal atrophy. These results suggest that heat shock factor-1 influences the pathological lesion selectivity in spinal and bulbar muscular atrophy.
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U2 - 10.1038/ncomms2417
DO - 10.1038/ncomms2417
M3 - Article
C2 - 23360996
AN - SCOPUS:84879154600
VL - 4
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1405
ER -