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Striatal long noncoding RNA Abhd11os is neuroprotective against an N-terminal fragment of mutant huntingtin in vivo.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2015 Mar; Vol. 36 (3), pp. 1601.e7-16. Date of Electronic Publication: 2014 Dec 18. - Publication Year :
- 2015
-
Abstract
- A large number of gene products that are enriched in the striatum have ill-defined functions, although they may have key roles in age-dependent neurodegenerative diseases affecting the striatum, especially Huntington disease (HD). In the present study, we focused on Abhd11os, (called ABHD11-AS1 in human) which is a putative long noncoding RNA (lncRNA) whose expression is enriched in the mouse striatum. We confirm that despite the presence of 2 small open reading frames (ORFs) in its sequence, Abhd11os is not translated into a detectable peptide in living cells. We demonstrate that Abhd11os levels are markedly reduced in different mouse models of HD. We performed in vivo experiments in mice using lentiviral vectors encoding either Abhd11os or a small hairpin RNA targeting Abhd11os. Results show that Abhd11os overexpression produces neuroprotection against an N-terminal fragment of mutant huntingtin, whereas Abhd11os knockdown is protoxic. These novel results indicate that the loss lncRNA Abhd11os likely contribute to striatal vulnerability in HD. Our study emphasizes that lncRNA may play crucial roles in neurodegenerative diseases.<br /> (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Disease Models, Animal
Female
Humans
Huntingtin Protein
Huntington Disease metabolism
Male
Mice, Inbred C57BL
RNA, Small Interfering genetics
RNA, Untranslated metabolism
Reverse Transcriptase Polymerase Chain Reaction
Serine Proteases metabolism
Corpus Striatum metabolism
Down-Regulation genetics
Gene Expression genetics
Gene Expression Regulation genetics
Huntington Disease genetics
Mutation
Nerve Tissue Proteins genetics
Neuroprotective Agents
Nuclear Proteins genetics
RNA, Untranslated genetics
Serine Proteases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 36
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 25619660
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2014.11.014