Retinoid X receptors (RXRs) present a subgroup of the nuclear receptor superfamily with particularly high evolutionary conservation of ligand binding domain. The receptor exists in α, β, and γ isotypes that form homo-/heterodimeric complexes with other permissive and non-permissive receptors. While research has identified the biochemical roles of several nuclear receptor family members, the roles of RXRs in various neurological disorders remain relatively under-investigated. RXR acts as ligand-regulated transcription factor, modulating the expression of genes that plays a critical role in mediating several developmental, metabolic, and biochemical processes. Cumulative evidence indicates that abnormal RXR signalling affects neuronal stress and neuroinflammatory networks in several neuropathological conditions. Protective effects of targeting RXRs through pharmacological ligands have been established in various cell and animal models of neuronal injury including Alzheimer disease, Parkinson disease, glaucoma, multiple sclerosis, and stroke. This review summarises the existing knowledge about the roles of RXR, its interacting partners, and ligands in CNS disorders. Future research will determine the importance of structural and functional heterogeneity amongst various RXR isotypes as well as elucidate functional links between RXR homo- or heterodimers and specific physiological conditions to increase drug targeting efficiency in pathological conditions.
Keywords: Alzheimer disease; Bexarotene; Endogenous ligands; Exogenous ligands; Glaucoma; Glucose metabolism; Heterodimerisation; Lipid X receptor (LXR); Lipid metabolism ligand; Multiple sclerosis; Neuroinflammation; Neuronal stress; Neuroprotection; Nuclear receptor-related 1 (Nurr1); Nuclear receptors; Parkinson disease; Peroxisome proliferator-activated receptor (PPAR); Retinoid X receptor (RXR); Stroke.
© 2021. The Author(s).