Development of Molecular Targeted Disease Modifying Therapy for Polyglutamine Diseases

脊髓和球性肌萎缩症（Spinal and bulbar muscular atrophy， SBMA）是一种由雄激素受体（AR）基因CAG三核苷酸扩增引起的运动神经元疾病。突变AR的核积累引发SBMA运动神经元的变性。我们的研究结果表明，自噬在SBMA中起保护作用，一种激活分子伴侣和自噬的小化合物抑制了SBMA中运动神经元的退化。我们还证明，在SBMA小鼠中外源性补充上调的miRNA可以减轻突变ar介导的运动神经元变性。

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.