Mechanisms of FUS Toxicity in Animal and Cellular Models of ALS/FTD.

Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s Disease) is a fatal disease of motor neurons. Mutations in the gene FUS cause familial and sporadic forms ALS, and FUS pathology is also found in the related neurodegenerative disorder, frontotemporal dementia (FTD). In novel animal and cellular models of ALS, this project will elucidate toxic gain-of-function mechanisms by which mutant FUS causes motor neuron and frontotemporal degeneration. This effort will test one promising approach to the treatment of FUS-ALS and FTD, and provide important insights that will lead to the development of other novel therapies.