FUS-related proteinopathies: Lessons from animal models

The recent identification of ALS-linked mutations in FUS and TDP-43 has led to a major shift in our thinking in regard to the potential molecular mechanisms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). RNA-mediated proteinopathy is increasingly being recognized as a potential cause of neurodegenerative disorders. PUS and TDP-43 are structurally and functionally similar proteins. FUS is a DNA/RNA binding protein that may regulate aspects of RNA metabolism, including splicing, mRNA processing, and micro RNA biogenesis. It is unclear how ALS-linked mutations perturb the functions of PUS. This review highlights recent advances in understanding the functions of FUS and discusses findings from PUS animal models that provide several key insights into understanding the molecular mechanisms that might contribute to ALS pathogenesis. Published by Elsevier B.V.