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

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State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_68B5A747F76C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation.
Journal
Cell reports
Author(s)
Pircs K., Petri R., Madsen S., Brattås P.L., Vuono R., Ottosson D.R., St-Amour I., Hersbach B.A., Matusiak-Brückner M., Lundh S.H., Petersén Å., Déglon N., Hébert S.S., Parmar M., Barker R.A., Jakobsson J.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
07/08/2018
Peer-reviewed
Oui
Volume
24
Number
6
Pages
1397-1406
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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.
Keywords
Argonaute Proteins/genetics, Autophagy/physiology, Humans, Huntington Disease/genetics, MicroRNAs/metabolism, Argonaute-2, Huntington’s disease, autophagy, microRNA, protein aggregation
Pubmed
Web of science
Open Access
Yes
Create date
14/08/2018 11:41
Last modification date
30/01/2020 6:20
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