title: Retinoids as potential targets for Alzheimer's disease.
abstract: Vitamin A and its derivatives, the retinoids, modulate several physiological and pathological processes through their interactions with nuclear retinoid receptor proteins termed as retinoic acid receptors (RARs) and retinoid X receptors (RXRs). An increasing body of evidence signifies the existence of retinoid signaling in diverse brain areas including cortex, amygdala, hypothalamus, hippocampus, and striatum suggesting its involvement in adult brain functions. Defective retinoid signaling has been evidenced in the pathology of Alzheimer's disease. Reports demonstrate that vitamin A deprived mice exhibit serious defects in spatial learning and memory signifying its importance in the maintenance of memory functions. Retinoid signaling impacts the development of AD pathology through multiple pathways. Ligand activation of RAR and RXR in APP/PS1 transgenic mice ameliorated the symptoms of AD and reduced amyloid accumulation and tau hyperphosphorylation. Retinoids also reduce the production of pro-inflammatory cytokines and chemokines by astrocytes and the microglia. Studies also suggest that neuronal cell lines treated with retinoid agonists exhibit an up-regulation in the expression and activity of choline acetyltransferase (ChAT). Reports depict that retinoic acid isomers enhance, the expression of genes linked with cholesterol efflux e.g. apoe, abca-1 and abcg-1 proteins in astrocytes. Furthermore numerous studies also indicate antioxidant potential of retinoids. Through this review we concisely summarize the biology of retinoids, emphasizing on their probable neuroprotective mechanisms that will help to elucidate the pivotal role of these receptors in AD pathology.
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India.
authors.forename: Rupinder K
authors.initials: RK
authors.lastname: Sodhi
authors.affiliation: Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002 Punjab, India. Electronic address: nirmal_puru@rediffmail.com.
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D012176:Retinoids
keywords: Alzheimer's disease; Amyloid; ApoE; Oxidative stress; Retinoids