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Genistein, a natural product derived from soybeans, ameliorates polyglutamine‐mediated motor neuron disease
Author(s) -
Qiang Qiang,
Adachi Hiroaki,
Huang Zhe,
Jiang YueMei,
Katsuno Masahisa,
Minamiyama Makoto,
Doi Hideki,
Matsumoto Shinjiro,
Kondo Naohide,
Miyazaki Yu,
Iida Madoka,
Tohnai Genki,
Sobue Gen
Publication year - 2013
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/jnc.12172
Subject(s) - spinal and bulbar muscular atrophy , androgen receptor , polyglutamine tract , motor neuron , biology , spinal cord , genistein , neuron , medicine , endocrinology , transgene , microbiology and biotechnology , mutant , neuroscience , genetics , gene , prostate cancer , cancer , huntingtin
Abstract Spinal and bulbar muscular atrophy ( SBMA ) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor ( AR ) gene. The pathologic features of SBMA are motor neuron loss in the spinal cord and brainstem, and diffuse nuclear accumulation and nuclear inclusions of mutant AR in residual motor neurons and certain visceral organs. AR ‐associated coregulator 70 ( ARA 70) was the first coregulator of AR to be identified, and it has been shown to interact with AR and increase its protein stability. Here, we report that genistein, an isoflavone found in soy, disrupts the interaction between AR and ARA 70 and promotes the degradation of mutant AR in neuronal cells and transgenic mouse models of SBMA . We also demonstrate that dietary genistein ameliorates behavioral abnormalities, improves spinal cord and muscle pathology, and decreases the amounts of monomeric AR and high‐molecular‐weight mutant AR protein aggregates in SBMA transgenic mice. Thus, genistein treatment may be a potential therapeutic approach for alleviating the symptoms of SBMA by disrupting the interactions between AR and ARA 70.