Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor ne uron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The charact...Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor ne uron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The characteristic pathological f inding is nuclear inclusions (NIs) consisting of mutant AR with an expanded poly Q in residual motor neurons, and in certain visceral organs. We immunohistochemi cally examined 11 SBMA patients at autopsy with 1C2, an antibody that specifical ly recognizes expanded polyQ.Our study demonstrated that diffuse nuclear accumul ation of mutant AR was far more frequent and extensive than NIs being distribute d in a wide array of CNS nuclei, and in more visceral organs than thus far belie ved. Mutant AR accumulation was also present in the cytoplasm, particularly in t he Golgi apparatus; nuclear or cytoplasmic predominance of accumulation was tiss ue 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 repe at length. Thus, diffuse nuclear accumulation of mutant AR apparently is a cardi nal pathogenetic process underlying neurological manifestations, as in SBMA tran sgenic mice, while cytoplasmic accumulation may also contribute to SBMA pathophy siology.展开更多
文摘Spinal and bulbar muscular atrophy (SBMA) is an inherited adult onset motor ne uron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor (AR), affecting only males. The characteristic pathological f inding is nuclear inclusions (NIs) consisting of mutant AR with an expanded poly Q in residual motor neurons, and in certain visceral organs. We immunohistochemi cally examined 11 SBMA patients at autopsy with 1C2, an antibody that specifical ly recognizes expanded polyQ.Our study demonstrated that diffuse nuclear accumul ation of mutant AR was far more frequent and extensive than NIs being distribute d in a wide array of CNS nuclei, and in more visceral organs than thus far belie ved. Mutant AR accumulation was also present in the cytoplasm, particularly in t he Golgi apparatus; nuclear or cytoplasmic predominance of accumulation was tiss ue 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 repe at length. Thus, diffuse nuclear accumulation of mutant AR apparently is a cardi nal pathogenetic process underlying neurological manifestations, as in SBMA tran sgenic mice, while cytoplasmic accumulation may also contribute to SBMA pathophy siology.
