title: Clinical features and molecular mechanisms of spinal and bulbar muscular atrophy (SBMA).
abstract: Spinal and bulbar muscular atrophy (SBMA) is an adult-onset neurodegenerative disease characterized by slowly progressive muscle weakness and atrophy. The cause of this disease is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine tract, within the first exon of the androgen receptor (AR) gene. SBMA exclusively occurs in adult males, whereas both heterozygous and homozygous females are usually asymptomatic. Lower motor neurons in the anterior horn of the spinal cord and those in the brainstem motor nuclei are predominantly affected in SBMA, and other neuronal and nonneuronal tissues are also widely involved to some extent. Testosterone-dependent nuclear accumulation of the pathogenic AR protein has been considered to be a fundamental step of neurodegenerative process, which is followed by several molecular events such as transcriptional dysregulation, axonal transport disruption and mitochondrial dysfunction. Results of animal studies suggest that androgen deprivation and activation of protein quality control systems are potential therapies for SBMA.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. ka2no@med.nagoya-u.ac.jp
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D019680:Trinucleotide Repeat Expansion
chemical_list: D011944:Receptors, Androgen