Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: A pathogenic marker

Haruhiko Banno, Hiroaki Adachi, Masahisa Katsuno, Keisuke Suzuki, Naoki Atsuta, Hirohisa Watanabe, Fumiaki Tanaka, Manabu Doyu, Gen Sobue

研究成果: Article査読

48 被引用数 (Scopus)

抄録

Objective: Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The nuclear accumulation of mutant AR is central to the pathogenesis of SBMA. Androgen deprivation with leuprorelin inhibits mutant AR accumulation, resulting in rescue of neuronal dysfunction in a mouse model of SBMA. This study aimed to investigate whether mutant AR accumulation in the scrotal skin is an appropriate biomarker of SBMA. Methods: Immunohistochemistry of both scrotal skin and the spinal cord was performed on five autopsied SBMA cases. Neurological severity and scrotal skin findings were studied in another 13 patients. Five other patients received subcutaneous injections of leuprorelin and underwent scrotal skin biopsy. Results: The degree of mutant AR accumulation in scrotal skin epithelial cells tended to be correlated with that in the spinal motor neurons in autopsy specimens, and it was well correlated with CAG repeat length and inversely correlated with the amyotrophic lateral sclerosis functional scale. Leuprorelin treatment inhibited mutant AR protein accumulation in the scrotal skin of SBMA patients. Interpretation: These observations suggest that scrotal skin biopsy findings are a potent pathogenic marker of SBMA and can be a surrogate end point in therapeutic trials.

本文言語English
ページ(範囲)520-526
ページ数7
ジャーナルAnnals of Neurology
59
3
DOI
出版ステータスPublished - 03-2006
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経学
  • 臨床神経学

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