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Omi / HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington’s disease
Author(s) -
Inagaki Reina,
Tagawa Kazuhiko,
Qi MeiLing,
Enokido Yasushi,
Ito Hikaru,
Tamura Takuya,
Shimizu Shigeomi,
Oyanagi Kityomitsu,
Arai Nobutaka,
Kanazawa Ichiro,
Wanker Erich E,
Okazawa Hitoshi
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06323.x
Subject(s) - huntingtin , huntington's disease , biology , huntingtin protein , gene silencing , mutant , neuroscience , neuron , neurodegeneration , western blot , genetically modified mouse , microbiology and biotechnology , transgene , disease , genetics , pathology , gene , medicine
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.