Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy.

ABSTRACT:

Background

A G₄C₂ hexanucleotide repeat expansion in the noncoding region of C9orf72 is the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). Putative disease mechanisms underlying c9FTD/ALS include toxicity from sense G₄C₂ and antisense G₂C₄ repeat-containing RNA, and from dipeptide repeat (DPR) proteins unconventionally translated from these RNA products.

Methods

Intracerebroventricular injections with adeno-associated virus (AAV) encoding 2 or 149 G₄C₂ repeats were performed on postnatal day 0, followed by assessment of behavioral and neuropathological phenotypes.

Results

Relative to control mice, gliosis and neurodegeneration accompan

SUBMITTER: Chew J 

PROVIDER: S-EPMC6377782 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature