RRC ID 2397
Author Adachi H, Katsuno M, Minamiyama M, Waza M, Sang C, Nakagomi Y, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Yoshida M, Hashizume Y, Sobue G.
Title Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients.
Journal Brain
Abstract Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The characteristic pathological finding is nuclear inclusions (NIs) consisting of mutant AR with an expanded polyQ in residual motor neurons, and in certain visceral organs. We immunohistochemically examined 11 SBMA patients at autopsy with 1C2, an antibody that specifically recognizes expanded polyQ. Our study demonstrated that diffuse nuclear accumulation of mutant AR was far more frequent and extensive than NIs being distributed in a wide array of CNS nuclei, and in more visceral organs than thus far believed. Mutant AR accumulation was also present in the cytoplasm, particularly in the Golgi apparatus; nuclear or cytoplasmic predominance of accumulation was tissue specific. Furthermore, the extent of diffuse nuclear accumulation of mutant AR in motor and sensory neurons of the spinal cord was closely related to CAG repeat length. Thus, diffuse nuclear accumulation of mutant AR apparently is a cardinal pathogenetic process underlying neurological manifestations, as in SBMA transgenic mice, while cytoplasmic accumulation may also contribute to SBMA pathophysiology.
Volume 128(Pt 3)
Pages 659-70
Published 2005-3-1
DOI 10.1093/brain/awh381
PII awh381
PMID 15659427
MeSH Aged Aged, 80 and over Cell Nucleus / metabolism Cytoplasm / metabolism Humans Immunoenzyme Techniques Intranuclear Inclusion Bodies / metabolism Intranuclear Inclusion Bodies / ultrastructure Male Middle Aged Muscular Atrophy, Spinal / genetics Muscular Atrophy, Spinal / metabolism* Muscular Atrophy, Spinal / pathology Mutation Organelles / metabolism Peptides / metabolism Receptors, Androgen / genetics* Receptors, Androgen / metabolism Tissue Distribution
IF 11.337
Times Cited 133
Mice RBRC00344