Lieberman Andrew P
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, United States.
Handb Clin Neurol. 2018;148:625-632. doi: 10.1016/B978-0-444-64076-5.00040-5.
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein. Studies of the pathology of SBMA subjects have revealed nuclear aggregates of the mutant androgen receptor, loss of lower motor neurons in the brainstem and spinal cord, and both neurogenic and myopathic changes in skeletal muscle. Mechanisms underlying disease pathogenesis include toxicity in both lower motor neurons and skeletal muscle, where effects on transcription, intracellular transport, and mitochondrial function have been documented. Therapies to treat SBMA patients remain largely supportive, although experimental approaches targeting androgen action or promoting degradation of the mutant androgen receptor protein or the encoding RNA are under active study.
脊髓延髓肌肉萎缩症（SBMA）是一种成人起病的神经肌肉系统退行性疾病，会导致近端肢体和延髓肌肉逐渐出现进行性无力和萎缩。该疾病由雄激素受体氨基末端的CAG/谷氨酰胺序列扩增引起。SBMA仅影响男性，这反映出关键致病事件是激素依赖性的。这些事件包括多聚谷氨酰胺雄激素受体从细胞质易位至细胞核以及突变蛋白的解折叠。对SBMA患者的病理学研究揭示了突变雄激素受体的核内聚集体、脑干和脊髓中运动神经元的丧失，以及骨骼肌中的神经源性和肌病性改变。疾病发病机制包括下运动神经元和骨骼肌中的毒性作用，其中已记录到对转录、细胞内运输和线粒体功能的影响。尽管针对雄激素作用、促进突变雄激素受体蛋白或编码RNA降解的实验性方法正在积极研究中，但治疗SBMA患者的疗法在很大程度上仍为支持性疗法。
