Type I PRMT inhibition protects against C9ORF72 arginine-rich dipeptide repeat toxicity

Published: May 22, 2020, 2 a.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.20.106260v1?rss=1 Authors: Premasiri, A. S., Gill, A. L., Vieira, F. G. Abstract: The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a repeat expansion mutation in the C9orf72 gene. Repeat-associated non-AUG (RAN) translation of this expansion produces five species of dipeptide repeat proteins (DRPs). The arginine containing DRPs, polyGR and polyPR, are consistently reported to be the most toxic. Here, we uncover Type I protein arginine methyltransferase (PRMT) inhibitors as possible therapeutics for polyGR- and polyPR- related toxicity. Furthermore, we reveal data that suggest that asymmetric dimethylation (ADMe) of polyGR is a determining factor in its pathogenesis. Copy rights belong to original authors. Visit the link for more info