中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (11): 1880-1892.doi: 10.4103/1673-5374.259604

• 综述:退行性病与再生 • 上一篇    下一篇

类视黄醇在预防阿尔茨海默病的神经炎症和神经变性中的潜在治疗作用

  

  • 出版日期:2019-11-15 发布日期:2019-11-15

Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease

Bhaskar C. Das 1 , Somsankar Dasgupta 2 , Swapan K. Ray 3   

  1. 1 Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
    2 Department of Neuroscience and Regenerative Medicine, Institute of Molecular Medicine and Genetics, Augusta University, Augusta, GA, USA
    3 Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Swapan K. Ray, PhD, swapan.ray@uscmed.sc.edu.
  • Supported by:

    The work was supported in part by an award from the Soy Health Research Program (SHRP, United Soybean Board, Chesterfield, MO, USA) (to SKR), a grant (SCIRF-2015-I-01) from South Carolina Spinal Cord Injury Research Fund (Columbia, SC, USA) (to SKR), and earlier R01 grants (CA-091460, and NS-057811) (to SKR) from the National Institutes of Health (Bethesda, MD, USA).

摘要:

orcid: 0000-0003-1734-542X(Swapan K. Ray)

Abstract:

All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid (RA) signaling is extremely important in the central nervous system. Impairment of RA signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired RA signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease (AD), which is pathologically characterized by extra-neuronal accumulation of amyloid plaques (aggregated amyloid-beta) and intra-neurofibrillary tangles (hyperphosphorylated tau protein) in the temporal lobe of the brain. AD is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in AD patients. Deficiency or deprivation of RA in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemokines and neuroinflammatory cytokines in microglia and astrocytes, which are activated in AD. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of AD in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in AD.

Key words: Alzheimer’s disease, amyloid plaques, neurofibrillary tangles, neuroinflammation, neurodegeneration, retinoids