Tamibarotene: A Candidate Retinoid Drug for Alzheimer’s Disease
Open accessAbstract
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.
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Vitamin A and retinoic acid administration improve Alzheimer's disease and age-related attenuation of memory/learning in mouse models, probably due to immunomodulatory effect and reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as promotion of differentiation of neural stem cells and regeneration of neural cells.
“Vitamin A and retinoic acid (a metabolite of all-trans-retinol) administration have been demonstrated to improve AD and age-related attenuation of memory/learning in mouse models, and this is probably due to their immunomodulatory effect and the reduction of pro-inflammatory cytokines and chemokines production by astrocytes and microglia, as well as to the promotion of differentiation of neural st”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [110]
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References 65 · Cited by 91
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- Authors
- Fukasawa, H., Nakagomi, M., Yamagata, N., Katsuki, H., Kawahara, K., Kitaoka, K., Miki, T., & Shudo, K.
- Affiliations
- Research Foundation ITSUU Laboratory (JP)
- Kumamoto University (JP)
- Tokushima University (JP)
- Osaka City University (JP)
- Venue
- Biological and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2012
- Volume
- 35
- Issue
- 8
- Pages
- 1206-1212
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2095082246
- Cited by
- 91
- References
- 65
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 14 · 2022: 9 · 2021: 7 · 2020: 9 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 9 · 2015: 2 · 2014: 6 · 2013: 6
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (24659118)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- tamibarotene, Am80, retinoids, Alzheimer's disease, retinoic acid receptor agonists, amyloid-beta deposition, APP23 mice, SAMP8 mice, acetylcholine, anxiety, insufficient sleep, scopolamine-induced amnesia, neuroinflammation, astrocytes, microglia, experimental autoimmune encephalomyelitis, neural stem cell differentiation, spinal cord injury, vascular factors, acute promyelocytic leukemia
- MeSH terms
- Alzheimer Disease, Animals, Benzoates, Brain, Humans, Tetrahydronaphthalenes, Transcription, Genetic, Receptors, Retinoic Acid
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