[In vitro aggregation and cellular toxicity of mutant androgen receptor protein in spinal and bulbar muscular atrophy].
Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor caused by expansion of a polyglutamine repeat within the androgen receptor(AR). We have studied the mutant AR in an in vitro system, and find aggregation of the AR protein to occur in a polyglutamine repeat length-dependent manner and the cellular toxicity to be coupled to aggregation. In addition we find intranuclear inclusions in nonneural tissues as well as affected neural tissues. These results indicate that the polyglutamine repeat length-dependent aggregation may be a likely molecular basis for the toxic gain of AR function that produces neuronal degeneration in SBMA. However, there is a recent report which suggests that inclusions did not correlate with cell death. Thus the mechanism of toxic gain of function remains to be elucidated.
Kobayashi
Y
Y
Department of Neurology, Nagoya University School of Medicine.
Li
M
M
Sobue
G
G
D016923:Cell Death / Q000502:physiology; D003603:Cytotoxins / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism*; D010455:Peptides / Q000502:physiology; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D018911:Trinucleotide Repeats / Q000235:genetics*
D003603:Cytotoxins; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine