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Emerging Evidence on Membrane Estrogen Receptors as Novel Therapeutic Targets for Central Nervous System Pathologies

Agnieszka Wnuk1, Karolina Przepiórska1, Bernadeta Angelika Pietrzak1

  • 1Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343 Krakow, Poland.

International Journal of Molecular Sciences
|February 25, 2023
PubMed

Insights

Estrogen signaling via membrane receptors (mERs) offers neuroprotection without nuclear ER side effects. Non-GPER-dependent mERs show promise for treating neurodegenerative diseases and stroke.

Area of Science:

  • Endocrinology
  • Neuroscience
  • Pharmacology

Background:

  • Estrogen signaling involves nuclear and membrane receptors (mERs) with distinct functions.
  • Membrane ERs (mERs) mediate rapid signaling and neuroprotection, unlike classical nuclear ERs.
  • G protein-coupled estrogen receptor 1 (GPER1) has shown benefits but is linked to tumorigenesis, prompting interest in other mERs.

Purpose of the Study:

  • To explore the therapeutic potential of non-GPER-dependent membrane estrogen receptors (mERs).
  • To investigate the neuroprotective and cognitive-enhancing roles of mERα and mERβ.
  • To highlight mERs as novel targets for treating neurological disorders.

Main Methods:

  • Review of existing literature on estrogen receptor signaling pathways.
  • Analysis of studies investigating GPER1 and non-GPER-dependent mERs (mERα, mERβ).
  • Evaluation of the impact of mERs on neuroprotection, synaptic plasticity, and cognitive function.

Main Results:

  • Non-GPER-dependent mERs, specifically mERα and mERβ, demonstrate protective effects against brain damage and cognitive decline.
  • These receptors influence synaptic plasticity, memory, and metabolic and vascular homeostasis.
  • mERs interact with noncoding RNAs and regulate gene translation in brain tissue.

Conclusions:

  • Non-GPER-dependent mERs offer neuroprotection and cognitive benefits without the adverse effects of nuclear ERs.
  • These receptors represent promising therapeutic targets for stroke and neurodegenerative diseases.
  • Targeting mERs could lead to novel pharmacotherapies for central nervous system disorders.
Keywords:
Alzheimer’s diseasemERmembrane estrogen receptorsnervous systemneuroprotectionrapid estrogen signalingstroke

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