Abstract

Amyotrophic Lateral Sclerosis (ALS) is a rare neurodegenerative disease that involves protein-aggregate formation, axonal retreat, and death of motor neurons. Despite many individual genes and gene mutations found to be common across ALS patients, the underlying cause and disease promoting cellular mechanisms are unknown. Mutations in one of these proteins, Fused in Sarcoma (FUS), have been found to account for 4% of familial ALS cases. The two mutations of interest are FUS-P525L, a highly prevalent mutation in aggressive cases of juvenile onset ALS, and a novel ALS-related mutant, FUS-P525R, which is at the same position and has shown similar effects. The functional impact of these mutations has not been well studied, but mutations in this region are known cause the protein to mislocalize from the nucleus to the cytoplasm. Once in the cytoplasm, mutant FUS is available to interact with many other proteins, resulting in the creation of degradation resistant protein aggregates that accumulate in the cell. This research involves creating the FUS P525L and FUS P525R mutations for expression in a neuronal cell line to study resulting protein aggregates, viability, and functionality of an ‘infected’ cell. The FUS P525L mutation was created and transfected into HEK 293 cells for assaying.

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