A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen

Simona Federica Spampinato, Sara Merlo, Ferdinando Nicoletti, Maria Angela Sortino

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Estrogen exerts neuroprotective activity under different experimental conditions through classical nuclear receptors, but mainly receptors expressed at the cell surface. Transducing mechanisms activated by these membrane estrogen receptors in the brain have been intensely investigated and, among others, interaction with G-protein coupled, metabotropic glutamate (mGlu) receptors has been considered. Besides mediating physiological estrogen functions, such as regulation of hormone production or sexual behavior in the hypothalamus, mGlu receptors, specifically mGlu1 receptor subtype, take part to the protective effect of estrogen in a model of neuronal toxicity induced by β-amyloid peptide. Coupling of estrogen receptor to mGlu1 receptor is supported by co-immunoprecipitation, similar neuroprotective effect induced by either receptor activation, lack of additivity when the two receptors are activated at the same time and prevention of the protective effect when antagonists of the other receptor are used, i.e. reduction of the protective effect of estrogen by the mGlu1 receptor antagonist and vice versa. In addition, the phosphatidylinositol-3 kinase/Akt pathway may represent the common signaling pathway to produce neuroprotection. These data introduce a novel view of the mechanisms underlying the neuroprotective activity of estrogen and open new perspectives also for future pharmacological interventions.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalMolecular and Cellular Pharmacology
Volume4
Issue number2
DOIs
Publication statusPublished - 2012

Fingerprint

Neuroprotective Agents
Estrogens
Metabotropic Glutamate Receptors
Estrogen Receptors
Phosphatidylinositol 3-Kinase
Cytoplasmic and Nuclear Receptors
GTP-Binding Proteins
Immunoprecipitation
Amyloid
Sexual Behavior
Hypothalamus
Hormones
Pharmacology
Peptides
Membranes
metabotropic glutamate receptor type 1
Brain

Keywords

  • Alzheimer's disease
  • Estrogen
  • Neurodegenerative disease
  • Neuroprotection
  • Phosphatidylinositol-3 kinase
  • Receptor transactivation

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Biology

Cite this

A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen. / Spampinato, Simona Federica; Merlo, Sara; Nicoletti, Ferdinando; Sortino, Maria Angela.

In: Molecular and Cellular Pharmacology, Vol. 4, No. 2, 2012, p. 61-67.

Research output: Contribution to journalArticle

Spampinato, Simona Federica ; Merlo, Sara ; Nicoletti, Ferdinando ; Sortino, Maria Angela. / A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen. In: Molecular and Cellular Pharmacology. 2012 ; Vol. 4, No. 2. pp. 61-67.
@article{668253923bb641bf9d09f835ed42346f,
title = "A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen",
abstract = "Estrogen exerts neuroprotective activity under different experimental conditions through classical nuclear receptors, but mainly receptors expressed at the cell surface. Transducing mechanisms activated by these membrane estrogen receptors in the brain have been intensely investigated and, among others, interaction with G-protein coupled, metabotropic glutamate (mGlu) receptors has been considered. Besides mediating physiological estrogen functions, such as regulation of hormone production or sexual behavior in the hypothalamus, mGlu receptors, specifically mGlu1 receptor subtype, take part to the protective effect of estrogen in a model of neuronal toxicity induced by β-amyloid peptide. Coupling of estrogen receptor to mGlu1 receptor is supported by co-immunoprecipitation, similar neuroprotective effect induced by either receptor activation, lack of additivity when the two receptors are activated at the same time and prevention of the protective effect when antagonists of the other receptor are used, i.e. reduction of the protective effect of estrogen by the mGlu1 receptor antagonist and vice versa. In addition, the phosphatidylinositol-3 kinase/Akt pathway may represent the common signaling pathway to produce neuroprotection. These data introduce a novel view of the mechanisms underlying the neuroprotective activity of estrogen and open new perspectives also for future pharmacological interventions.",
keywords = "Alzheimer's disease, Estrogen, Neurodegenerative disease, Neuroprotection, Phosphatidylinositol-3 kinase, Receptor transactivation",
author = "Spampinato, {Simona Federica} and Sara Merlo and Ferdinando Nicoletti and Sortino, {Maria Angela}",
year = "2012",
doi = "10.4255/mcpharmacol.12.06",
language = "English",
volume = "4",
pages = "61--67",
journal = "Molecular and Cellular Pharmacology",
issn = "1938-1247",
publisher = "Lumitext Publishing",
number = "2",

}

TY - JOUR

T1 - A main role for metabotropic glutamate receptor 1 in the neuroprotective effect of estrogen

AU - Spampinato, Simona Federica

AU - Merlo, Sara

AU - Nicoletti, Ferdinando

AU - Sortino, Maria Angela

PY - 2012

Y1 - 2012

N2 - Estrogen exerts neuroprotective activity under different experimental conditions through classical nuclear receptors, but mainly receptors expressed at the cell surface. Transducing mechanisms activated by these membrane estrogen receptors in the brain have been intensely investigated and, among others, interaction with G-protein coupled, metabotropic glutamate (mGlu) receptors has been considered. Besides mediating physiological estrogen functions, such as regulation of hormone production or sexual behavior in the hypothalamus, mGlu receptors, specifically mGlu1 receptor subtype, take part to the protective effect of estrogen in a model of neuronal toxicity induced by β-amyloid peptide. Coupling of estrogen receptor to mGlu1 receptor is supported by co-immunoprecipitation, similar neuroprotective effect induced by either receptor activation, lack of additivity when the two receptors are activated at the same time and prevention of the protective effect when antagonists of the other receptor are used, i.e. reduction of the protective effect of estrogen by the mGlu1 receptor antagonist and vice versa. In addition, the phosphatidylinositol-3 kinase/Akt pathway may represent the common signaling pathway to produce neuroprotection. These data introduce a novel view of the mechanisms underlying the neuroprotective activity of estrogen and open new perspectives also for future pharmacological interventions.

AB - Estrogen exerts neuroprotective activity under different experimental conditions through classical nuclear receptors, but mainly receptors expressed at the cell surface. Transducing mechanisms activated by these membrane estrogen receptors in the brain have been intensely investigated and, among others, interaction with G-protein coupled, metabotropic glutamate (mGlu) receptors has been considered. Besides mediating physiological estrogen functions, such as regulation of hormone production or sexual behavior in the hypothalamus, mGlu receptors, specifically mGlu1 receptor subtype, take part to the protective effect of estrogen in a model of neuronal toxicity induced by β-amyloid peptide. Coupling of estrogen receptor to mGlu1 receptor is supported by co-immunoprecipitation, similar neuroprotective effect induced by either receptor activation, lack of additivity when the two receptors are activated at the same time and prevention of the protective effect when antagonists of the other receptor are used, i.e. reduction of the protective effect of estrogen by the mGlu1 receptor antagonist and vice versa. In addition, the phosphatidylinositol-3 kinase/Akt pathway may represent the common signaling pathway to produce neuroprotection. These data introduce a novel view of the mechanisms underlying the neuroprotective activity of estrogen and open new perspectives also for future pharmacological interventions.

KW - Alzheimer's disease

KW - Estrogen

KW - Neurodegenerative disease

KW - Neuroprotection

KW - Phosphatidylinositol-3 kinase

KW - Receptor transactivation

UR - http://www.scopus.com/inward/record.url?scp=84871863169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871863169&partnerID=8YFLogxK

U2 - 10.4255/mcpharmacol.12.06

DO - 10.4255/mcpharmacol.12.06

M3 - Article

VL - 4

SP - 61

EP - 67

JO - Molecular and Cellular Pharmacology

JF - Molecular and Cellular Pharmacology

SN - 1938-1247

IS - 2

ER -