Human Molecular Genetics, Vol 7, 693-701, Copyright © 1998 by Oxford University Press
DE Merry, Y Kobayashi, CK Bailey, AA Taye and KH Fischbeck
Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease
caused by the expansion of a polyglutamine repeat within the androgen
receptor (AR). We have studied the mutant AR in an in vitro system, and
find both aggregation and proteolytic processing of the AR protein to occur
in a polyglutamine repeat length-dependent manner. In addition, we find the
aberrant metabolism of expanded repeat AR to be coupled to cellular
toxicity, indicating a likely molecular basis for the toxic gain of AR
function that produces neuronal degeneration in SBMA.
ARTICLES
Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. merryd@mail.med.upenn.edu
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