HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer's disease (AD) are available, but none on its relationship with the cholinergic system and neurotrophic factors as well as other AD-related proteins. In this study, immunohistochemical analyses revealed that AD patients had a higher cytosolic distribution of OMI/HTRA2 protein compared to controls. Quantitative analyses on brain extracts indicated a significant increase in the active form of OMI/HTRA2 in the AD brain. Activated OMI/HTRA2 protein positively correlated with stress-associated read-through acetylcholinesterase activity. In addition, alpha 7 nicotinic acetylcholine receptor gene expression, a receptor also known to be localized on the outer membrane of mitochondria, showed a strong correlation with OMI/HTRA2 gene expression in three different brain regions. Interestingly, the activated OMI/HTRA2 levels also correlated with the activity of the acetylcholinebiosynthesizing enzyme, choline acetyltransferase (ChAT); with levels of the neurotrophic factors, NGF and BDNF; with levels of the soluble fragments of amyloid precursor protein (APP); and with gene expression of the microtubule-associated protein tau in the examined brain regions. Overall, the results demonstrate increased levels of the mitochondrial serine protease OMI/ HTRA2, and a coherent pattern of association between the activated form of OMI/HTRA2 and several key proteins involved in AD pathology. In this paper, we propose a new hypothetical model to highlight the importance and needs of further investigation on the role of OMI/HTRA2 in the mitochondrial function and AD.
机构:
Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
Institute of Precision Medicine, Xiangya Hospital, Xiangya Medical School, Central South UniversityLaboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
Kai Fu
Yanfei Wang
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Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow UniversityLaboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
Yanfei Wang
Dongkai Guo
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Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow UniversityLaboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
Dongkai Guo
Guanghui Wang
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Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow UniversityLaboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
Guanghui Wang
Haigang Ren
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Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow UniversityLaboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuropsychiatric Disorders, Department of Pharmacology,College of Pharmaceutical Sciences, Soochow University
机构:
Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Park, Hye-Min
Kim, Goo-Young
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Catholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Catholic Univ Korea, Coll Med, Dept Biomed Sci, Seoul 137701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Kim, Goo-Young
Nam, Min-Kyung
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Catholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Catholic Univ Korea, Coll Med, Dept Biomed Sci, Seoul 137701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Nam, Min-Kyung
Seong, Geun-Hye
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Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Seong, Geun-Hye
Han, Chul
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Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Han, Chul
Chung, Kwang Chul
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Yonsei Univ, Dept Biol, Coll Life Sci & Biotechnol, Seoul 120749, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Chung, Kwang Chul
Kang, Seongman
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Korea Univ, Sch Life Sci & Biotechnol, Seoul 136701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Kang, Seongman
Rhim, Hyangshuk
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Catholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
Catholic Univ Korea, Coll Med, Dept Biomed Sci, Seoul 137701, South KoreaCatholic Univ Korea, Res Inst Mol Genet, Seoul 137701, South Korea
机构:
Catholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South KoreaCatholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South Korea
Hur, Wonhee
Kang, Byung Yoon
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Catholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South KoreaCatholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South Korea
Kang, Byung Yoon
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Kim, Sung Min
Lee, Gil Won
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Catholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South KoreaCatholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South Korea
Lee, Gil Won
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Kim, Jung-Hee
Nam, Min-Kyung
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Catholic Univ Korea, Coll Med, Dept Biomed & Hlth Sci, Seoul 06591, South KoreaCatholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South Korea
Nam, Min-Kyung
Rhim, Hyangshuk
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Catholic Univ Korea, Coll Med, Dept Biomed & Hlth Sci, Seoul 06591, South KoreaCatholic Univ Korea, Coll Med, Liver Res Ctr, Catholic Univ, Seoul 06591, South Korea
机构:
Bilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USABilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Gulsuner, Hilal Unal
Gulsuner, Suleyman
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Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USABilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Gulsuner, Suleyman
Mercan, Fatma Nazli
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机构:
Ankara Univ, Fac Med, Dept Neurol, TR-06100 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Mercan, Fatma Nazli
Onat, Onur Emre
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Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Onat, Onur Emre
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Walsh, Tom
Shahin, Hashem
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Bethlehem Univ, Dept Life Sci, Bethlehem 92248, PalestineBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Shahin, Hashem
Lee, Ming K.
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Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USABilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Lee, Ming K.
Dogu, Okan
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Mersin Univ, Fac Med, Dept Neurol, TR-33343 Mersin, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Dogu, Okan
Kansu, Tulay
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机构:
Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Kansu, Tulay
Topaloglu, Haluk
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Hacettepe Univ, Fac Med, Dept Pediat, Neurol Unit, TR-06100 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Topaloglu, Haluk
Elibol, Bulent
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Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Elibol, Bulent
Akbostanci, Cenk
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Ankara Univ, Fac Med, Dept Neurol, TR-06100 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Akbostanci, Cenk
King, Mary-Claire
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机构:
Univ Washington, Dept Med, Seattle, WA 98195 USA
Univ Washington, Dept Genome Sci, Seattle, WA 98195 USABilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
King, Mary-Claire
Ozcelik, Tayfun
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机构:
Bilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey
Ozcelik, Tayfun
Tekinay, Ayse B.
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Bilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, TurkeyBilkent Univ, Natl Nanotechnol Res Ctr UNAM, Inst Mat Sci & Nanotechnol, TR-06800 Ankara, Turkey