Title: Perindopril, a centrally active angiotensin‐converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease
Abstract: The FASEB JournalVolume 25, Issue 9 p. 2911-2920 Research CommunicationFree to Read Perindopril, a centrally active angiotensin-converting enzyme inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease Yi-Fei Dong, Yi-Fei Dong Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorKeiichiro Kataoka, Keiichiro Kataoka Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorYoshiko Tokutomi, Yoshiko Tokutomi Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorHisato Nako, Hisato Nako Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorTaishi Nakamura, Taishi Nakamura Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorKensuke Toyama, Kensuke Toyama Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorDaisuke Sueta, Daisuke Sueta Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorNobutaka Koibuchi, Nobutaka Koibuchi Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorEiichiro Yamamoto, Eiichiro Yamamoto Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorHisao Ogawa, Hisao Ogawa Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorShokei Kim-Mitsuyama, Corresponding Author Shokei Kim-Mitsuyama [email protected] Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanCorrespondence: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1–1-1 Honjyo, Kumamoto 860–8556, Japan. E-mail: [email protected]Search for more papers by this author Yi-Fei Dong, Yi-Fei Dong Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorKeiichiro Kataoka, Keiichiro Kataoka Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorYoshiko Tokutomi, Yoshiko Tokutomi Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorHisato Nako, Hisato Nako Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorTaishi Nakamura, Taishi Nakamura Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorKensuke Toyama, Kensuke Toyama Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorDaisuke Sueta, Daisuke Sueta Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorNobutaka Koibuchi, Nobutaka Koibuchi Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorEiichiro Yamamoto, Eiichiro Yamamoto Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorHisao Ogawa, Hisao Ogawa Department of Cardiovascular Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanSearch for more papers by this authorShokei Kim-Mitsuyama, Corresponding Author Shokei Kim-Mitsuyama [email protected] Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, JapanCorrespondence: Department of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, 1–1-1 Honjyo, Kumamoto 860–8556, Japan. E-mail: [email protected]Search for more papers by this author First published: 18 May 2011 https://doi.org/10.1096/fj.11-182873Citations: 102 This article includes supplemental data. Please visit http://www.fasebj.org to obtain this information. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT The purpose of this work was to test whether brain-penetrating angiotensin-converting enzyme (ACE) inhibitors (e.g., perindopril), as opposed to non-brain-penetrating ACE inhibitors (e.g., enalapril and imidapril), may reduce the cognitive decline and brain injury in Alzheimer's disease (AD). We first compared the effect of perindopril, enalapril, and imidapril on cognitive impairment and brain injury in a mouse model of AD induced by intracerebroventricular (i.c.v.) injection of amyloid-β (Aβ)1–40. Perindopril, with significant inhibition of hippocampal ACE, significantly prevented cognitive impairment in this AD mouse model. This beneficial effect was attributed to the suppression of microglia/astrocyte activation and the attenuation of oxidative stress caused by iNOS induction and extracellular superoxide dismutase down-regulation. In contrast, neither enalapril nor imidapril prevented cognitive impairment and brain injury in this AD mouse. We next examined the protective effects of perindopril on cognitive impairment in PS2APP-transgenic mice overexpressing Aβ in the brain. Perindopril, without affecting brain Aβ deposition, significantly suppressed the increase in hippocampal ACE activity and improved cognition in PS2APP-transgenic mice, being associated with the suppression of hippocampal astrocyte activation and attenuation of superoxide. Our data demonstrated that the brain-penetrating ACE inhibitor perindopril, as compared to non-brain-penetrating ACE inhibitors, protected against cognitive impairment and brain injury in experimental AD models.—Dong, Y. -F., Kataoka, K., Tokutomi, Y., Nako, H., Nakamura, T., Toyama, K., Sueta, D., Koibuchi, N., Yamamoto, E., Ogawa, H., Kim-Mitsuyama, S. 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Publication Year: 2011
Publication Date: 2011-05-18
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 129
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