Investigating the Molecular Mechanisms of RNA Binding Protein ARPP21 in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disease characterised by the degeneration of motor neurons in the brain and spinal cord, leading to muscle denervation, weakness, and atrophy. Whole exome sequencing studies have identified a novel RNA-binding protein (RBP) ARPP21, which is highly expressed in neurons. Preliminary data suggest that ARPP21 is a dynamic protein that regulates protein translation and forms pulsatile granules in neurons. This pulsatile activity is unique and has not been observed in any other RBP, indicating a distinctive function for ARPP21. Mutations in ARPP21 lead to dysregulated granule formation and potentially reduced protein translation in neurons. This project aims to elucidate the role of ARPP21 in protein translation, the reasons behind granule formation in neurons, and the molecular mechanisms underlying granule dysregulation and translation in ALS.