Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement

• Published in: Molecular neurobiology Vol. 59; no. 4; pp. 2027 - 2050
• Main Authors: Sharma, Samridhi, Shen, Ting, Chitranshi, Nitin, Gupta, Veer, Basavarajappa, Devaraj, Sarkar, Soumalya, Mirzaei, Mehdi, You, Yuyi, Krezel, Wojciech, Graham, Stuart L., Gupta, Vivek
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2022; Springer Nature B.V; Humana Press
• Subjects: Alzheimer's disease; Animal models; Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Evolutionary conservation; Gene Expression Regulation; Glaucoma; Inflammation; Isotypes; Life Sciences; Ligands; Movement disorders; Multiple sclerosis; Nervous System Diseases; Neurobiology; Neurodegenerative diseases; Neurological diseases; Neurology; Neurons and Cognition; Neuropathology; Neurosciences; Parkinson's disease; Receptors, Cytoplasmic and Nuclear - metabolism; Retinoid X receptors; Retinoid X Receptors - metabolism; Structure-function relationships; Therapeutic targets; Lipid metabolism ligand; Glaucoma; Neuroprotection; Bexarotene; Multiple sclerosis; Stroke; Endogenous ligands; Alzheimer disease; Parkinson disease; Neuroinflammation; Lipid X receptor (LXR); Nuclear receptors; Neuronal stress; Exogenous ligands; Glucose metabolism; Nuclear receptor-related 1 (Nurr1); Retinoid X receptor (RXR); Peroxisome proliferator-activated receptor (PPAR); Heterodimerisation; Neuroinfammation
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-021-02709-y

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.