Aberrant RNA homeostasis in amyotrophic lateral sclerosis: potential for new therapeutic targets?

Document Type

Article

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. The disease pathogenesis is multifaceted in that multiple cellular and molecular pathways have been identified as contributors to the disease progression. Consequently, numerous therapeutic targets have been pursued for clinical development, unfortunately with little success. The recent discovery of mutations in RNA modulating genes such as TARDBP/TDP-43, FUS/TLS or C9ORF72 changed our understanding of neurodegenerative mechanisms in ALS and introduced the role of dysfunctional RNA processing as a significant contributor to disease pathogenesis. This article discusses the latest findings on such RNA toxicity pathways in ALS and potential novel therapeutic approaches.

Keywords

ALS, ALS therapeutics, C9ORF72, repeat expansion, RNA toxicity, TDP-43

Publication Date

1-1-2014

Publication Title

Neurodegenerative disease management

E-ISSN

17582032

Volume

4

Issue

6

First Page

417

Last Page

437

PubMed ID

25531686

Digital Object Identifier (DOI)

10.2217/nmt.14.36

Share

COinS