Development of Molecular Targeted Disease Modifying Therapy for Polyglutamine Diseases

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Spinal and bulbar muscular atrophy (SBMA)is a motor neuron disease caused by an expansion of CAG trinucleotide expansion with in the androgen receptor (AR) gene. Nuclear accumulation of mutant AR triggers the degeneration of motor neurons in SBMA. Our results indicate that autophagy plays a protective role in SBMA, and that a small compound activating both molecular chaperones and autophagy suppresses the motor neuron degeneration in this disease. We also demonstrated that exogenous supplementation of miRNA that is up-regulated in SBMA mice attenuates mutant AR-mediated motor neuron degeneration.