Neuromuscular dysfunction in patient-derived FUS^R244RR-ALS iPSC model via axonal downregulation of neuromuscular junction proteins.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition characterized by the progressive degeneration of motor neurons (MNs), ultimately resulting in death due to respiratory failure. A common feature among ALS cases is the early loss of axons, pointing to defects in axonal transport and translation as initial disease indicators. ALS is associated with mutations in RNA-binding proteins, such as FUS (Fused in Sarcoma). Here, we established a FUS^R244RR-ALS hiPSC-derived model that recapitulates the MN survival and muscle contractility defects characteristic of ALS patients. Analysis of the protein and mRNA expression profiles in axonal and somatodendritic compartments of ALS-afflicted and isogenic control MNs revealed a selective downregulation of proteins essential f

SUBMITTER: von Kugelgen N 

PROVIDER: S-EPMC12429959 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature