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Gene & Protein in Disease GPER1 in brain and heart diseases

research. Based on the mediation of genomic and non- Funding
genomic rapid signaling and the ubiquitous expression
of GPER1 in the excitable tissue, GPER1 plays a crucial None.
role in several neurological and cardiovascular diseases Conflict of interest
(Figures 1 and 2). In particular, its exclusive protective
role in multiple processes of cardiovascular diseases is The authors declare that they have no conflicts of interest.
obvious, including cardiovascular function, hypertension,
hypertrophy, AF, and cardiovascular fibrosis. However, Author contributions
the previous studies have not consistently reported Conceptualization: Beatrice A. Nossek
beneficial effects of GPER1 on both sexes. This is because Visualization: Beatrice A. Nossek
in hypertrophy, males gained an advantage from GPER1 Writing–original draft: All authors
activation, whereas in hypertension, vasodilatation and AF Writing–review & editing: All authors
data suggest marked positive effects in females (Figure 2).
Equivalently, GPER1 activation may be highly favorable in Ethics approval and consent to participate
almost all neurological diseases discussed in this review, Not applicable.
including neuroinflammation, depression and mood
disorders, schizophrenia, MS, ASD, AD, PD, and ADHD Consent for publication
as well as learning and memory. Studies have emphasized
a more favorable influence of GPER1 on females with AD, Not applicable.
whereas males with PD have benefited more from GPER1.
However, results regarding the impact of GPER1 activation Availability of data
on epilepsy, depression and mood disorders, and migraine Not applicable.
and pain are controversial, and not only advantageous
but also disadvantageous effects have been described References
(Figure 1). Nonetheless, GPER1 appears to be a promising 1. Ziemka-Nalecz M, Pawelec P, Ziabska K, Zalewska T. Sex
candidate for further investigations, considering its use differences in brain disorders. Int J Mol Sci. 2023;24:19.
as a neuroprotective target in several disorders of the
CNS. Furthermore, in cardiovascular and neurological doi: 10.3390/ijms241914571
diseases, particularly in depression and mood disorders, 2. Singh R, Nasci VL, Guthrie G, et al. Emerging roles for G
schizophrenia, ASD, ADHD, and hypertension, serum protein-coupled estrogen receptor 1 in cardio-renal health:
GPER1 level was analyzed as a predictor of the respective Implications for aging. Biomolecules. 2022;12(3):412.
disorder (Table 1). In this regard, studies have reported doi: 10.3390/biom12030412
elevated GPER1 serum levels in both sexes of patients 3. da Silva JS, Montagnoli TL, Rocha BS, et al. Estrogen
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with depression and mood disorders, whereas elevated receptors: Therapeutic perspectives for the treatment of
GPER1 levels were detected only in male patients with cardiac dysfunction after myocardial infarction. Int J Mol
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reduced GPER1 serum levels were detected in both
sexes. This is because in hypertrophy, reduced GPER1 doi: 10.3390/ijms22020525
levels were detected only in postmenopausal women with 4. Dinh QN, Vinh A, Arumugam TV, Drummond GR,
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199
GPER1 in these disorders as well as emphasize GPER1 target to treat cardiovascular disease in a sex-specific
as a possible diagnostic marker. GPER1 appears to be a manner? Br J Pharmacol. 2021;178(19):3849-3863.
promising target for developing novel therapeutics for doi: 10.1111/bph.15521
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with sex-specific approaches. However, further clinical disease and atherosclerotic risk factors: Estrogen and
studies are warranted to confirm the promising results beyond. Can J Cardiol. 2020;36(5):706-711.
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obtain a better knowledge of sex-specific pathology and doi: 10.1016/j.cjca.2020.03.002
future treatment options. 6. Groban L, Tran QK, Ferrario CM, et al. Female heart health:
Is GPER the missing link? Front Endocrinol (Lausanne).
Acknowledgments 2019;10:919.
None. doi: 10.3389/fendo.2019.00919

Volume 4 Issue 1 (2025) 16 doi: 10.36922/gpd.4632