Neuropathology and therapeutic intervention in spinal and bulbar muscular atrophy.
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 histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA.
Banno
Haruhiko
H
Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Japan. banno@med.nagoya-u.ac.jp
Katsuno
Masahisa
M
Suzuki
Keisuke
K
Tanaka
Fumiaki
F
Sobue
Gen
G
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D009134:Muscular Atrophy, Spinal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D018911:Trinucleotide Repeats
D018931:Antineoplastic Agents, Hormonal; D006360:Heat-Shock Proteins; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine; D013739:Testosterone; D016729:Leuprolide