Tamibarotene: A Candidate Retinoid Drug for Alzheimer’s Disease
スポンサーリンク
概要
- 論文の詳細を見る
Tamibarotene (Am80), a synthetic retinoid approved in Japan for treatment of acute promyelocytic leukemia (APL), is a retinoic acid receptor (RAR) agonist with high specificity for RARα and RARβ over RARγ. Temporarily and spatially specific expression of RARs suggests their pivotal roles in the adult brain. Am80 is considered to be a promising candidate drug for treatment of Alzheimer’s disease (AD) because of its transcriptional controls of multiple target genes involved in etiology and pathology of AD. In APP23 AD model mice, administration of Am80 decreased the deposition of insoluble amyloid-β(42). In senescence-accelerated mice (SAMP8), Am80 ameliorated the decrease of cortical acetylcholine, as well as reducing anxiety in behavioral tests and improving the sleep deficit. Am80 also effected a significant improvement of memory in the rat scopolamine-induced memory deficit model. Like other retinoids, Am80 also has an immunomodulatory effect and reduces secretion of proinflammatory cytokines and chemokines by astrocytes and microglia surrounding amyloid-β plaques. In a rat experimental autoimmune encephalomyelitis model, Am80 reduced inflammatory cytokines and showed significant efficacy. Retinoids also promote differentiation of neural stem cells, and Am80 improved the recovery of spinal cord-injured rats. Am80 may also improve vascular factors involved in onset and/or progression of AD. Am80 has been in clinical use for treatment of APL in Japan since 2005, and has been reported to have fewer side effects than other retinoids. We have recently started a clinical study to evaluate the efficacy and safety of Am80 for the treatment of Alzheimer’s disease.
著者
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SHUDO Koichi
Research Foundation Itsuu Laboratory
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Miki Takami
Department Of Geriatric Medicine Osaka City University Graduate School Of Medicine
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KAWAHARA Kohichi
Department of Molecular Cell Function, Graduate School of Medical and Pharmaceutical Sciences, Kumam
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Katsuki Hiroshi
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Nakagomi Madoka
Research Foundation Itsuu Laboratory
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Kitaoka Kazuyoshi
Department Of Integrative Physiology Graduate School Of Medicine The University Of Tokushima
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Miki Takami
Department of Geriatrics and Neurology, Graduate School of Medicine, Osaka City University
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Fukasawa Hiroshi
Research Foundation ITSUU Laboratory
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Yamagata Naoko
Research Foundation ITSUU Laboratory
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Katsuki Hiroshi
Department of Chemico-Pharmacological Sciences, Kumamoto University
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Kitaoka Kazuyoshi
Department of Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School
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