Omi/HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington's disease

Reina Inagaki, Kazuhiko Tagawa, Mei Ling Qi, Yasushi Enokido, Hikaru Ito, Takuya Tamura, Shigeomi Shimizu, Kityomitsu Oyanagi, Nobutaka Arai, Ichiro Kanazawa, Erich E. Wanker, Hitoshi Okazawa

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Selective vulnerability of neurons is a critical feature of neurodegenerative diseases, but the underlying molecular mechanisms remain largely unknown. We here report that Omi/HtrA2, a mitochondrial protein regulating survival and apoptosis of cells, decreases selectively in striatal neurons that are most vulnerable to the Huntington's disease (HD) pathology. In microarray analysis, Omi/HtrA2 was decreased under the expression of mutant huntingtin (htt) in striatal neurons but not in cortical or cerebellar neurons. Mutant ataxin-1 (Atx-1) did not affect Omi/HtrA2 in any type of neuron. Western blot analysis of primary neurons expressing mutant htt also confirmed the selective reduction of the Omi/HtrA2 protein. Immunohistochemistry with a mutant htt-transgenic mouse line and human HD brains confirmed reduction of Omi/HtrA2 in striatal neurons. Overexpression of Omi/HtrA2 by adenovirus vector reverted mutant htt-induced cell death in primary neurons. These results collectively suggest that the homeostatic but not proapoptotic function of Omi/HtrA2 is linked to selective vulnerability of striatal neurons in HD pathology.

Original languageEnglish (US)
Pages (from-to)30-40
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number1
StatePublished - Jul 2008
Externally publishedYes


  • Cell death
  • Huntingtin
  • Huntington's disease
  • Mitochondria
  • Omi/HtrA2
  • Polyglutamine


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