Pircs, Karolina, Petri, Rebecca, Madsen, Sofia, Brattås, Per Ludvik, Vuono, Romina, Ottosson, Daniella R., St-Amour, Isabelle, Hersbach, Bob A., Matusiak-Brückner, Monika, Lundh, Sofia Hult, and others. (2018) Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation. Cell Reports, 24 (6). pp. 1397-1406. ISSN 2211-1247. (doi:10.1016/j.celrep.2018.07.017) (KAR id:78969)
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| Official URL: https://doi.org/10.1016/j.celrep.2018.07.017 |
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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.
| Item Type: | Article |
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| DOI/Identification number: | 10.1016/j.celrep.2018.07.017 |
| Uncontrolled keywords: | Huntington’s disease, autophagy, microRNA, Argonaute-2, protein aggregation, Medway School of Pharmacy |
| Divisions: | Divisions > Division of Natural Sciences > Medway School of Pharmacy |
| Depositing User: | Romina Vuono |
| Date Deposited: | 25 Nov 2019 15:27 UTC |
| Last Modified: | 05 Nov 2024 12:43 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/78969 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Vuono, Romina.
| Creator's ORCID: |
 https://orcid.org/0000-0002-5162-3422
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