Cited by 58Alzheimer's disease research and treatmentsRetinoids in leukemia and cellular processesDementia and Cognitive Impairment Research

Molecular Signaling Mechanisms of Natural and Synthetic Retinoids for Inhibition of Pathogenesis in Alzheimer’s Disease

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Chakrabarti, Mrinmay, McDonald, Alexander J., Will Reed, J., Moss, Melissa A., Das, Bhaskar C., Ray, Swapan K.·2016·Journal of Alzheimer's Disease

Abstract

Retinoids, which are vitamin A derivatives, interact through retinoic acid receptors (RARs) and retinoid X receptors (RXRs) and have profound effects on several physiological and pathological processes in the brain. The presence of retinoic acid signaling is extensively detected in the adult central nervous system, including the amygdala, cortex, hypothalamus, hippocampus, and other brain areas. Retinoids are primarily involved in neural patterning, differentiation, and axon outgrowth. Retinoids also play a key role in the preservation of the differentiated state of adult neurons. Impairment in retinoic acid signaling can result in neurodegeneration and progression of Alzheimer’s disease (AD). Recent studies demonstrated severe deficiencies in spatial learning and memory in mice during retinoic acid (vitamin A) deprivation indicating its significance in preserving memory function. Defective cholinergic neurotransmission plays an important role in cognitive deficits in AD. All-trans retinoic acid is known to enhance the expression and activity of choline acetyltransferase in neuronal cell lines. Activation of RAR and RXR is also known to impede the pathogenesis of AD in mice by inhibiting accumulation of amyloids. In addition, retinoids have been shown to inhibit the expression of chemokines and pro-inflammatory cytokines in microglia and astrocytes, which are activated in AD. In this review article, we have described the chemistry and molecular signaling mechanisms of natural and synthetic retinoids and current understandings of their therapeutic potentials in prevention of AD pathology.

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  • In experimental models of AD, RA inhibited oxidative damage and mitochondrial dysfunction; increased ApoE expression and suppressed inflammation; and improved learning and memory.

    “In experimental models of AD, RA: (1) inhibited oxidative damage and mitochondrial dysfunction; (2) increased ApoE expression and suppressed inflammation; and (3) improved learning and memory84,85.”

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Authors
Chakrabarti, M., McDonald, A. J., Will Reed, J., Moss, M. A., Das, B. C., & Ray, S. K.
Affiliations
  • University of South Carolina (US)
  • Department of Chemical Engineering, University of South Carolina, Columbia, SC, USA
  • University of Kansas Medical Center (US)
Corresponding author
Ray, Swapan K.
Venue
Journal of Alzheimer's Disease
Published
2016-01-22
Volume
50
Issue
2
Pages
335-352
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
OpenAlex
W2196629482
Cited by
57
References
155
Citations by year
2026: 3 · 2025: 7 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 2
FWCI
0.70
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • South Carolina Spinal Cord Injury Research Fund
  • School of Medicine, University of South Carolina
  • National Institute on Aging (P30AG035982)
  • National Institute of General Medical Sciences (P20GM103641)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
retinoids, Alzheimer's disease
MeSH terms
Alzheimer Disease, Animals, Brain, Humans, Neurons, Retinoids, Tretinoin, Signal Transduction, Retinoid X Receptors, Mice

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