期刊
CELL REPORTS
卷 24, 期 6, 页码 1397-1406出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.07.017
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资金
- NIHR award of a Biomedical Research Centre
- University of Cambridge
- Swedish Research Council [K2014-62X-22527-01-3, K2014-62X-20404-08-5]
- Swedish Foundation for Strategic Research [FFL12-0074]
- Swedish Brain Foundation [FO2014-0106]
- Swedish Excellence Project Basal Ganglia Disorders Linnaeus Consortium (Bagadilico)
- Swedish Government Initiative for Strategic Research Areas (MultiPark)
- Swedish Government Initiative for Strategic Research Areas (StemTherapy)
- Swedish Foundation for Strategic Research (SSF) [FFL12-0074] Funding Source: Swedish Foundation for Strategic Research (SSF)
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.
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