RNA-mediated Toxicity in C9orf72 ALS and FTD

Overview

Journal Neurobiol Dis

Specialty Neurology

Date 2020 Aug 24

PMID 32829028

Citations 21

Authors

Zachary T McEachin

Janani Parameswaran

Nisha Raj

Gary J Bassell

Jie Jiang

Affiliations

Soon will be listed here.

Abstract

A GGGGCC hexanucleotide repeat expansion in the first intron of C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Compelling evidence suggests that gain of toxicity from the bidirectionally transcribed repeat expanded RNAs plays a central role in disease pathogenesis. Two potential mechanisms have been proposed including RNA-mediated toxicity and/or the production of toxic dipeptide repeat proteins. In this review, we focus on the role of RNA mediated toxicity in ALS/FTD caused by the C9orf72 mutation and discuss arguments for and against this mechanism. In addition, we summarize how GC repeat RNAs can elicit toxicity and potential therapeutic strategies to mitigate RNA-mediated toxicity.

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