Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation.

TitleHuntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation.
Publication TypeJournal Article
Year of Publication2018
AuteursPircs, K, Petri, R, Madsen, S, Brattås, PLudvik, Vuono, R, Ottosson, DR, St-Amour, I, Hersbach, BA, Matusiak-Brückner, M, Lundh, SHult, Petersén, Å, Déglon, N, Hébert, SS, Parmar, M, Barker, RA, Jakobsson, J
JournalCell Rep
Volume24
Issue6
Pagination1397-1406
Date Published2018 Aug 07
ISSN2211-1247
Abstract

Many neurodegenerative diseases are characterized by the presence of intracellular protein aggregates, resulting in alterations in autophagy. However, the consequences of impaired autophagy for neuronal function remain poorly understood. In this study, we used cell culture and mouse models of huntingtin protein aggregation as well as post-mortem material from patients with Huntington's disease to demonstrate that Argonaute-2 (AGO2) accumulates in the presence of neuronal protein aggregates and that this is due to impaired autophagy. Accumulation of AGO2, a key factor of the RNA-induced silencing complex that executes microRNA functions, results in global alterations of microRNA levels and activity. Together, these results demonstrate that impaired autophagy found in neurodegenerative diseases not only influences protein aggregation but also directly contributes to global alterations of intracellular post-transcriptional networks.

DOI10.1016/j.celrep.2018.07.017
Alternate JournalCell Rep
PubMed ID30089251