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.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2009
Total Cost
$1,647,737
Indirect Cost
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State
Country
Zip Code
Bennett, Craig L; Dastidar, Somasish G; Ling, Shuo-Chien et al. (2018) Senataxin mutations elicit motor neuron degeneration phenotypes and yield TDP-43 mislocalization in ALS4 mice and human patients. Acta Neuropathol 136:425-443
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Manzano, Raquel; SorarĂº, Gianni; Grunseich, Christopher et al. (2018) Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease. J Neurol Neurosurg Psychiatry 89:808-812
Pourshafie, Naemeh; Lee, Philip R; Chen, Ke-Lian et al. (2018) Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents. J Vis Exp :
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Guber, Robert D; Takyar, Varun; Kokkinis, Angela et al. (2017) Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy. Neurology 89:2481-2490

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