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. Recently, the research has focused on three specific neuromuscular 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 myofibrillar myopathy caused by mutations in ZASP. Specific research accomplishments in the past year include the following: (1) evaluation of the effects of proteasome inhibitor treatment in a mouse model of SMA, (2) characterization of the effects of IGF-1 in an animal model of SBMA,(3) identification of interacting proteins for wild type and mutant ZASP and developing animal models with ZASP mutation.

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Cristofani, Riccardo; Crippa, Valeria; Rusmini, Paola et al. (2017) Inhibition of retrograde transport modulates misfolded protein accumulation and clearance in motoneuron diseases. Autophagy 13:1280-1303
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Foran, Emily; Kwon, Deborah Y; Nofziger, Jonathan H et al. (2016) CNS uptake of bortezomib is enhanced by P-glycoprotein inhibition: implications for spinal muscular atrophy. Neurobiol Dis 88:118-24
Hjelm, B E; Grunseich, C; Gowing, G et al. (2016) Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo. Gene Ther 23:424-37

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