학술논문
Alkannin Attenuates Amyloid β Aggregation and Alzheimer's Disease Pathology.
Document Type
Academic Journal
Author
Hosoi T; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.) hosoi@rs.socu.ac.jp ozawak@hiroshima-u.ac.jp.; Yazawa K; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.).; Imada M; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.).; Tawara A; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.).; Tohda C; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.).; Nomura Y; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.).; Ozawa K; Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Sanyo Onoda, Japan (T.H.); Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Minami-ku, Japan (K.Y., M.I., A.T., K.O.); Department of Pharmacology, Kurume University School of Medicine, Kurume, Japan (Y.N.); and Section of Neuromedical Science, Division of Bioscience, Institute of Natural Medicine, University of Toyama, Toyama, Japan (C.T.) hosoi@rs.socu.ac.jp ozawak@hiroshima-u.ac.jp.
Source
Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0035623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0111 (Electronic) Linking ISSN: 0026895X NLM ISO Abbreviation: Mol Pharmacol Subsets: MEDLINE
Subject
Language
English
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease that is accompanied by memory decline and cognitive dysfunction. Aggregated amyloid β formation and accumulation may be one of the underlying mechanisms of the pathophysiology of AD. Therefore, compounds that can inhibit amyloid β aggregation may be useful for treatment. Based on this hypothesis, we screened plant compounds used in Kampo medicine for chemical chaperone activity and identified that alkannin had this property. Further analysis indicated that alkannin could inhibit amyloid β aggregation. Importantly, we also found that alkannin inhibited amyloid β aggregation after aggregates had already formed. Through the analysis of circular dichroism spectra, alkannin was found to inhibit β -sheet structure formation, which is an aggregation-prone toxic structure. Furthermore, alkannin attenuated amyloid β -induced neuronal cell death in PC12 cells, ameliorated amyloid β aggregation in the AD model of Caenorhabditis elegans ( C. elegans ), and inhibited chemotaxis observed in AD C. elegans , suggesting that alkannin could potentially inhibit neurodegeneration in vivo. Overall, these results suggest that alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in AD. SIGNIFICANCE STATEMENT: Aggregated amyloid β formation and accumulation is one of the underlying mechanisms of the pathophysiology of Alzheimer's disease. We found that alkannin had chemical chaperone activity, which can inhibit β-sheet structure formation of amyloid β and its aggregation, neuronal cell death, and Alzheimer's disease phenotype in C. elegans. Overall, alkannin may have novel pharmacological properties for inhibiting amyloid β aggregation and neuronal cell death in Alzheimer's disease.
(Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)
(Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)