Suppressive effects of SuHeXiang Wan on Aβ42-induced extracellular signal-regulated kinaseERK hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease

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概要

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• SuHeXiang Wan (SHXW), a Chinese traditional medicine, has been used to treat infantile convulsions, seizures and strokes. Previously, we reported that modified SHXW, called KSOP1009, suppressed the hyper-activation of c-Jun N-terminal kinase (JNK) and Alzheimer's disease (AD)-like phenotypes in amyloid-β42 (Aβ42)-expressing Drosophila AD models. In the present study, we, further, investigated the detailed mechanism by which KSOP1009 suppresses the AD-like phenotypes of the model flies. As seen in the brains of AD patients, pan-neuronal expression of Aβ42 in Drosophila increased activation of extracellular signal-regulated kinase (ERK), which was monitored by its phosphorylation level, and the number of glial cells in the brain. Suppression of caspase activity did not affect these phenomena, suggesting that Aβ42 induces ERK activation and glial cell proliferation independently of apoptotic processes. KSOP1009 intake significantly reduced the level of ERK activation and the number of glial cells. Moreover, KSOP1009 intake also effectively decreased the defects in the wing vein formation induced by Epidermal growth factor receptor (Egfr) overexpression in fly wings, suggesting that it may contain an inhibitory substance that inhibits the EGFR/ERK signaling pathway. In addition, the Aβ42-induced locomotive defect was partially rescued by inhibition of the elevated ERK activity through its antagonistic drug treatment. Taken together, these results suggest that KSOP1009 exerts its therapeutic effect by inhibiting the EGFR/ERK pathway and glial cell proliferation and by suppressing the JNK pathway and apoptosis.

著者

• KOO Byung-Soo

  Department of Oriental Neuropsychiatry, College of Oriental Medicine, Dongguk University

• Hong Yoon

  Department Of Urology George Washington University School Of Medicine And Health Sciences

• Lee Im-soon

  Department Of Biological Sciences College Of Sciences Konkuk University Seoul Chungbuk National Univ

• Lee Soojin

  Department Of Microbiology Chungnam National University

• Bang Se

  Department Of Industry And Competition Policy Korea Development Institute

• Park Seung

  Department Of Anatomy College Of Medicine Konkuk University

• LEE Jang

  Department of Control and Instrumentation Engineering, and Automatic Control Research Center Seoul National University

• CHO Kyoung

  Department of Internal Medicine, Maryknoll Medical Center

• Park Seung

  Department of Biological Sciences, Konkuk University

• Hwang Soojin

  Department of Biological Sciences, Konkuk University

• Kim Young-Kyoon

  Department of Forest Products & Biotechnology, Kookmin University

• Kim Young-Kyoon

  Department of Forest Products & Biotechnology, Kookmin University

• Hong Yoon

  Department of Biological Sciences, Konkuk University

• Bang Se

  Department of Biological Sciences, Konkuk University

• Koo Byung-Soo

  Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University

• Lee Soojin

  Department of Biological Sciences, Konkuk University

• Lee Jang

  Department of Biological Sciences, Konkuk University

• Cho Kyoung

  Department of Biological Sciences, Konkuk University

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