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

作     者：Bhaskar C. Das Somsankar Dasgupta Swapan K. Ray 

作者机构：Department of MedicineIcahn School of Medicine at Mount SinaiNew YorkNYUSA Department of Neuroscience and Regenerative MedicineInstitute of Molecular Medicine and GeneticsAugusta UniversityAugustaGAUSA Department of PathologyMicrobiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSCUSA 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2019年第14卷第11期

页      面：1880-1892页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：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) earlier R01 grants(CA-091460,and NS-057811)(to SKR) from the National Institutes of Health(Bethesda,MD,USA) 

主　　题：Alzheimer's disease amyloid plaques neurofibrillary tangles neuroinflammation neurodegeneration retinoids 

摘      要：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 signaling is extremely important in the central nervous system. Impairment of retinoic acid 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 retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, 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. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid 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 Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease 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 Alzheimer’s disease.