Striatal long noncoding RNA Abhd11os is neuroprotective against an N-terminal fragment of mutant huntingtin in vivo

Neurobiol Aging. 2015 Mar;36(3):1601.e7-16. doi: 10.1016/j.neurobiolaging.2014.11.014. Epub 2014 Dec 18.


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.

Keywords: Gene regulation; Huntington disease; Neurodegeneration; Neuroprotection; Noncoding RNA; Striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Down-Regulation / genetics*
  • Female
  • Gene Expression / genetics*
  • Gene Expression Regulation / genetics*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mutation*
  • Nerve Tissue Proteins / genetics*
  • Neuroprotective Agents*
  • Nuclear Proteins / genetics*
  • RNA, Small Interfering / genetics
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serine Proteases / genetics*
  • Serine Proteases / metabolism


  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nuclear Proteins
  • RNA, Small Interfering
  • RNA, Untranslated
  • ABHD11 protein, human
  • Serine Proteases