MOLECULAR PATHOGENESIS STUDY OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) USING FUSED IN SARCOMA (FUS) PROTEIN

Abstract

ALS, as a specific disorder on neurodegeneration, causes the death of neurons which control voluntary muscles. A proposed mechanism on the pathogenesis of ALS is proteopathy performed by some specific proteins. In this research, we are aiming to study the molecular properties of FUS protein in biophysics way on three main subprojects. The first one is to reveal the overall structural features of the aggregation-prone FUS protein by truncating it into independent domains; then focus on the special RRM domain, and monitor its detailed mechanism over 𝛽-amyloid fibrillation. The second one is to reveal the mechanism of protein liquid-liquid phase separation (LLPS) of FUS protein, especially its prion-like domain. The last one is to characterize the potential possibility of FUS protein in the detriment to membrane system during conformational changes upon phase separation and amyloid fibrillation; then focus on the study of RRM domain in the interaction with mimic membrane systems.