Studies of Hereditary Neurological Disease: Disease Mechanisms

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The purpose of this research program is to investigate the mechanisms of hereditary neurological diseases, with the ultimate intent of developing effective treatments for these disorders. The research focuses on three specific motor neuron diseases: autosomal recessive spinal muscular atrophy (SMA) due to deficiency of the protein SMN, X-linked spinal and bulbar muscular atrophy (SBMA) due to polyglutamine expansion in the androgen receptor, and distal spinal muscular atrophy/Charcot-Marie-Tooth disease type 2D (CMT2D) caused by mutations in tRNA synthetase. Specific research accomplishments in the past year include the following: (1) characterization of the role of IGF-1 and Akt in a cell culture model of SBMA, (2) evaluation of the efficacy of histone deacetylase and proteasome inhibitor treatment in a mouse model of SMA, (3) studies of the disease mechanisms of CMT2D and other hereditary forms of neuropathy and distal spinal muscular atrophy, (4) studies of the role of profilin in polyglutamine disease.