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Widespread alterati...
Widespread alterations in microRNA biogenesis in human Huntington’s disease putamen
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- Petry, Serena (författare)
- Laval University
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- Keraudren, Rémi (författare)
- Laval University
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- Nateghi, Behnaz (författare)
- Laval University
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visa fler...
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- Loiselle, Andréanne (författare)
- Laval University
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- Pircs, Karolina (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups,Semmelweis University
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- Jakobsson, Johan (författare)
- Lund University,Lunds universitet,Molekylär neurogenetik,Forskargrupper vid Lunds universitet,Molecular Neurogenetics,Lund University Research Groups
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- Sephton, Chantelle (författare)
- Laval University
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- Langlois, Mélanie (författare)
- Laval University,Centre hospitalier universitaire de Québec
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- St-Amour, Isabelle (författare)
- Laval University
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- Hébert, Sébastien S. (författare)
- Laval University
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(creator_code:org_t)
- 2022-07-22
- 2022
- Engelska.
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Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 10
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Altered microRNA (miRNA) expression is a common feature of Huntington’s disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels. In this study, we sought to determine if miRNA maturation per se was compromised in HD. Towards this end, we characterized major miRNA biogenesis pathway components and miRNA maturation products (pri-miRNA, pre-miRNA, and mature) in human HD (N = 41, Vonsattel grades HD2-4) and healthy control (N = 25) subjects. Notably, the striatum (putamen) and cortex (BA39) from the same individuals were analyzed in parallel. We show that Ago2, Drosha, and Dicer were strongly downregulated in human HD at the early stages of the disease. Using a panel of HD-related miRNAs (miR-10b, miR-196b, miR-132, miR-212, miR-127, miR-128), we uncovered various types of maturation defects in the HD brain, the most prominent occurring at the pre-miRNA to mature miRNA maturation step. Consistent with earlier findings, we provide evidence that alterations in autophagy could participate in miRNA maturation defects. Notably, most changes occurred in the striatum, which is more prone to HTT aggregation and neurodegeneration. Likewise, we observed no significant alterations in miRNA biogenesis in human HD cortex and blood, strengthening tissue-specific effects. Overall, these data provide important clues into the underlying mechanisms behind miRNA alterations in HD-susceptible tissues. Further investigations are now required to understand the biological, diagnostic, and therapeutic implications of miRNA/RNAi biogenesis defects in HD and related neurodegenerative disorders.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Ago2
- Autophagy
- Biogenesis
- Dicer
- Huntington’s disease
- microRNA
- RNAi
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Petry, Serena
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Keraudren, Rémi
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Nateghi, Behnaz
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Loiselle, Andréa ...
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Pircs, Karolina
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Jakobsson, Johan
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visa fler...
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Sephton, Chantel ...
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Langlois, Mélani ...
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St-Amour, Isabel ...
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Hébert, Sébastie ...
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Neurovetenskaper
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Acta Neuropathol ...
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Lunds universitet