Abstract
The G-protein-coupled estrogen receptor-1 (GPER) is an extranuclear estrogen receptor that regulates the expression of several downstream signaling pathways with a variety of biological actions including cell migration, proliferation, and apoptosis in different parts of the brain area. It is endogenously activated by estrogen, a steroidal hormone that binds to GPER receptors which help in maintaining cellular homeostasis and neuronal integrity as well as influences neurogenesis. In contrast, neurodegenerative disorders are a big problem for society, and still many people suffer from motor and cognitive impairments. Research to date reported that GPER has the potential to whittle down motor abnormalities and cognitive dysfunction by limiting the progression of neurodegenerative disorders. Although several findings suggest that GPER activation accelerated transcription of the PI3K/Akt/Gsk-3β and ERK1/2 signaling pathway that halt disease progression by decreasing oxidative stress, neuroinflammation, and apoptosis. Accordingly, the goal of this review is to highlight the basic mechanism of GPER signaling pathway-mediated neuroprotection in various neurodegenerative disorders including Parkinson’s disease (PD), Huntington’s disease (HD), Tardive dyskinesia (TD), and Epilepsy. This review also discusses the role of the GPER activators which might be a promising therapeutic target option to treat neurodegenerative disorders. All the data were obtained from published articles in PubMed (353), Web of Science (788), and Scopus (770) databases using the search terms: GPER, PD, HD, TD, epilepsy, and neurodegenerative disorders.
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Data Availability
Enquiries about data availability should be directed to the authors.
Abbreviations
- AD:
-
Alzheimer’s disorders
- BDNF:
-
Brain-derived neurotrophic factor
- COX-2:
-
Cyclooxygenase-2
- ER-α:
-
Estrogen receptor alpha
- ER-β:
-
Estrogen receptor beta
- GPER1:
-
G-protein estrogen receptor-1
- GPR30:
-
G-protein-coupled estrogen receptor-30
- GSH:
-
Glutathione
- GSK-3β:
-
Glycogen synthase kinase-3 beta
- HD:
-
Huntington’s disease
- HO-1:
-
Heme oxygenase-1
- IL-1β:
-
Interleukin 1 beta
- iNOS:
-
Nitric oxide synthase
- MPTP:
-
1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B cells
- NMDA:
-
N-methyl-D-aspartic acid
- PD:
-
Parkinson’s disease
- SNpc:
-
Substantia nigra pars compacta
- TD:
-
Tardive dyskinesia
- TNF-α:
-
Tumor necrosis factor-alpha
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Acknowledgements
The authors would like to acknowledge the facility provided by the Central University of Punjab (CUPB), Bathinda, India, and Indian Council of Medical Research, New Delhi, India, for providing a Senior Research Fellowship to Mr. Shubham Upadhayay to pursue his research at the Department of Pharmacology, CUPB.
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SU contributed to data acquisition and concept design. RG contributed to manuscript drafting and data interpretation. SS contributed to manuscript writing and data acquisition. MM contributed to manuscript drafting. GS contributed to data interpretation. PK contributed to concept design, review of draft manuscript, and final approval of the manuscript.
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Upadhayay, S., Gupta, R., Singh, S. et al. Involvement of the G-Protein-Coupled Estrogen Receptor-1 (GPER) Signaling Pathway in Neurodegenerative Disorders: A Review. Cell Mol Neurobiol 43, 1833–1847 (2023). https://doi.org/10.1007/s10571-022-01301-9
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DOI: https://doi.org/10.1007/s10571-022-01301-9