PMID- 35015251
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220716
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 59
IP  - 4
DP  - 2022 Apr
TI  - Retinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a 
      Focus on Neuropathological Involvement.
PG  - 2027-2050
LID - 10.1007/s12035-021-02709-y [doi]
AB  - 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 alpha, beta, and gamma 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.
CI  - (c) 2021. The Author(s).
FAU - Sharma, Samridhi
AU  - Sharma S
AUID- ORCID: 0000-0002-1167-6511
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia. samridhi.sharma@mq.edu.au.
FAU - Shen, Ting
AU  - Shen T
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
FAU - Chitranshi, Nitin
AU  - Chitranshi N
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
FAU - Gupta, Veer
AU  - Gupta V
AD  - School of Medicine, Deakin University, Melbourne, VIC, Australia.
FAU - Basavarajappa, Devaraj
AU  - Basavarajappa D
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
FAU - Sarkar, Soumalya
AU  - Sarkar S
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
FAU - Mirzaei, Mehdi
AU  - Mirzaei M
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
FAU - You, Yuyi
AU  - You Y
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
AD  - Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
FAU - Krezel, Wojciech
AU  - Krezel W
AD  - Institut de Genetique Et de Biologie Moleculaire Et Cellulaire, INSERM U1258, 
      CNRS UMR 7104, Unistra, 67404, Illkirch-Graffenstaden, France.
FAU - Graham, Stuart L
AU  - Graham SL
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia.
AD  - Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
FAU - Gupta, Vivek
AU  - Gupta V
AD  - Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, 
      Macquarie University, Sydney, NSW, Australia. vivek.gupta@mq.edu.au.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220111
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Ligands)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptors)
SB  - IM
EIN - Mol Neurobiol. 2022 Mar 12;:. PMID: 35278210
MH  - Animals
MH  - Gene Expression Regulation
MH  - Ligands
MH  - *Nervous System Diseases
MH  - *Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Retinoid X Receptors/metabolism
PMC - PMC9015987
OTO - NOTNLM
OT  - Alzheimer disease
OT  - Bexarotene
OT  - Endogenous ligands
OT  - Exogenous ligands
OT  - Glaucoma
OT  - Glucose metabolism
OT  - Heterodimerisation
OT  - Lipid X receptor (LXR)
OT  - Lipid metabolism ligand
OT  - Multiple sclerosis
OT  - Neuroinflammation
OT  - Neuronal stress
OT  - Neuroprotection
OT  - Nuclear receptor-related 1 (Nurr1)
OT  - Nuclear receptors
OT  - Parkinson disease
OT  - Peroxisome proliferator-activated receptor (PPAR)
OT  - Retinoid X receptor (RXR)
OT  - Stroke
COIS- The authors declare no conflict of interest. W. K. is an inventor of the patent 
      family "Precursor compounds for providing retinoids of the vitamin A5 pathway and 
      uses thereof" PCT/HU2017/091937, US16102137, 127356JP-18340, 127578AU-18340, 
      127579CN-18340, and 128446CA-18340. W. K. is a shareholder of CISCAREX UG.
EDAT- 2022/01/12 06:00
MHDA- 2022/04/21 06:00
PMCR- 2022/01/11
CRDT- 2022/01/11 12:34
PHST- 2021/08/19 00:00 [received]
PHST- 2021/12/21 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2022/01/11 12:34 [entrez]
PHST- 2022/01/11 00:00 [pmc-release]
AID - 10.1007/s12035-021-02709-y [pii]
AID - 2709 [pii]
AID - 10.1007/s12035-021-02709-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2022 Apr;59(4):2027-2050. doi: 10.1007/s12035-021-02709-y. Epub 
      2022 Jan 11.