Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Oct;35(10):2421.e1-2421.e12.
doi: 10.1016/j.neurobiolaging.2014.04.015. Epub 2014 Apr 19.

Unconventional features of C9ORF72 expanded repeat in amyotrophic lateral sclerosis and frontotemporal lobar degeneration

Sabina Vatovec  1 , Anja Kovanda  2 , Boris Rogelj  3
Affiliations
Review

Unconventional features of C9ORF72 expanded repeat in amyotrophic lateral sclerosis and frontotemporal lobar degeneration

Sabina Vatovec et al. Neurobiol Aging. 2014 Oct.

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are devastating neurodegenerative diseases that form two ends of a complex disease spectrum. Aggregation of RNA binding proteins is one of the hallmark pathologic features of ALS and FTDL and suggests perturbance of the RNA metabolism in their etiology. Recent identification of the disease-associated expansions of the intronic hexanucleotide repeat GGGGCC in the C9ORF72 gene further substantiates the case for RNA involvement. The expanded repeat, which has turned out to be the single most common genetic cause of ALS and FTLD, may enable the formation of complex DNA and RNA structures, changes in RNA transcription, and processing and formation of toxic RNA foci, which may sequester and inactivate RNA binding proteins. Additionally, the transcribed expanded repeat can undergo repeat-associated non-ATG-initiated translation resulting in accumulation of a series of dipeptide repeat proteins. Understanding the basis of the proposed mechanisms and shared pathways, as well as interactions with known key proteins such as TAR DNA-binding protein (TDP-43) are needed to clarify the pathology of ALS and/or FTLD, and make possible steps toward therapy development.

Keywords: Amyotrophic lateral sclerosis; C9ORF72; Di-peptide repeats; Expanded G4C2 repeats; Frontotemporal lobar degeneration; G-quadruplex; I-motif; RAN translation; RNA foci; RNA toxicity; RNA-binding proteins; hnRNP.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources