Spinal and bulbar muscular atrophy.
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.
['Lieberman|Andrew P|AP|']
D000818:Animals D001933:Brain Stem D004195:Disease Models, Animal D006801:Humans D009046:Motor Neurons D009134:Muscular Atrophy, Spinal D010455:Peptides D011944:Receptors, Androgen D013116:Spinal Cord
spinal and bulbar muscular atrophy androgen receptor CAG/polyglutamine expansion neuromuscular disease testosterone