ReviewFUS-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. FUS 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 FUS. This review highlights recent advances in understanding the functions of FUS and discusses findings from FUS animal models that provide several key insights into understanding the molecular mechanisms that might contribute to ALS pathogenesis.

► The recent discoveries of ALS causative mutations in FUS and TDP-43 (both RNA-binding proteins) had major shift towards understanding molecular basis of ALS. ► The use of a wide range of FUS and TDP-43 animal models has led to a rapid advance in our knowledge. ► Availability of tool such as invertebrate and vertebrate models will help in identifying genetic and small molecule that might help in treating ALS.