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Huntingtin Aggregat...
Huntingtin Aggregation Impairs Autophagy, Leading to Argonaute-2 Accumulation and Global MicroRNA Dysregulation
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- Pircs, Karolina (author)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Petri, Rebecca (author)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Madsen, Sofia (author)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Brattås, Per Ludvik (author)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Vuono, Romina (author)
- University of Cambridge
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- Ottosson, Daniella R. (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- St-Amour, Isabelle (author)
- Laval University
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- Hersbach, Bob A. (author)
- Lund University
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- Matusiak-Brückner, Monika (author)
- Lund University
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- Lundh, Sofia Hult (author)
- Lund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups
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- Petersén, Åsa (author)
- Lund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups
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- Déglon, Nicole (author)
- Lausanne University Hospital
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- Hébert, Sébastien S. (author)
- Laval University
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- Parmar, Malin (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups
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- Barker, Roger A. (author)
- Lund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups,University of Cambridge
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- Jakobsson, Johan (author)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2018
- 2018
- English 10 s.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 24:6, s. 1397-1406
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http://www.cell.com/...
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Abstract
Subject headings
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- 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. Pircs et al. report that aggregation of the mutant huntingtin protein, a hallmark of Huntington's disease proteinopathy, impairs macroautophagy, leading to Argonaute-2 accumulation and global dysregulation of microRNAs. These results indicate that autophagy not only influences protein aggregation but also directly contributes to the global alterations of post-transcriptional networks in Huntington's disease.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Argonaute-2
- autophagy
- Huntington's disease
- microRNA
- protein aggregation
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Pircs, Karolina
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Petri, Rebecca
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Madsen, Sofia
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Brattås, Per Lud ...
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Vuono, Romina
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Ottosson, Daniel ...
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show more...
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St-Amour, Isabel ...
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Hersbach, Bob A.
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Matusiak-Brückne ...
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Lundh, Sofia Hul ...
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Petersén, Åsa
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Déglon, Nicole
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Hébert, Sébastie ...
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Parmar, Malin
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Barker, Roger A.
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Jakobsson, Johan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell Reports
- By the university
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Lund University