Frontiers in PharmacologyNeurosciencePeer-reviewed journal article
Type I PRMT inhibition protects against C9ORF72 arginine-rich dipeptide repeat toxicity
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.
- Citations
- 17
- FWCI
- 1.19
- Field percentile
- top 18%
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- C9orf72-derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility
Laura Fumagalli, Florence L. Young, … Philip Van Damme·Science AdvancesPeer-reviewed·Apr 9, 2021
- Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM
A. B. Loveland, E. Svidritskiy, … A. A. Korostelev·bioRxiv·Aug 30, 2020
- Divergent Molecular Pathways for Toxicity of Selected Mutant C9ORF72-derived Dipeptide Repeats
Sonia Okekenwa, Ming Ying Tsai, … Yuyu Song·bioRxiv·Sep 28, 2023
- Inhibiting toxicity of ALS-linked dipeptide repeat proteins by polystyrene sulfonate (PSS)
Anna Bratek‐Skicki, Junaid Ahmed, … Péter Tompa·bioRxiv·May 19, 2023
- C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress
M.E. Cicardi, Justin Hallgren, … Davide Trotti·iSciencePeer-reviewed·Jul 28, 2023
- Inflammasome mediated neuronal-microglial crosstalk: a therapeutic substrate for the familial C9orf72 variant of the frontotemporal dementia/amyotrophic lateral sclerosis
Kyle J. Trageser, Chad Smith, … Giulio Maria Pasinetti·bioRxiv·Jan 27, 2022