Protective Effects of G Protein-Coupled Estrogen Receptor 1 (GPER1) on β-Amyloid-Induced Neurotoxicity: Implications for Alzheimer’s Disease

Alzheimer’s disease (AD) is a problematic disease that has shown a significant increase in patient numbers worldwide. AD is identified pathologically by the accumulation of the toxic amyloid beta (Aβ) protein, neurofibrillary tangles and neuropil threads in postmortem brains of AD patients. Women are more prone to AD either due to their increased life expectancy or the decline in Estrogen hormone levels around menopause. Estrogens play a physiologically important role in the brain, but there is debate about the association between estrogen and Ad. The neuroprotective effects of estrogens are possibly mediated by estrogen receptors (ERs), which include classical nuclear estrogen receptors (ERα and ERβ) and nonclassical ER (G protein-coupled estrogen receptor 1, GPER1(GPR30)). The effect of GPER1 on Aβ-induced neurotoxicity is unclear. Here we studied the effect of GPER1 receptor agonists G-1 on rat neuronal cells. Rat neuronal cells were incubated with Aβ1–42, either alone or in combination with GPER1 agonist G-1 (10−7, 10−8 and 10−9 M). Cell viability was determined by MTT assays and apoptotic effects induced by Aβ1–42 were measured by Cell Death Detection kit. Oxidative stress parameters, including nitric oxide (NO) levels and total oxidant status (TOS) were measured by spectrophotometry. Approximately half of the cell death was observed with 10−6 M Aβ1–42 incubation for 48 hours. This is the first study that explores the effect of activation of GPER1 by its agonist G-1 on neuroprotection against Aβ1–42-toxicity in rat neuronal cells. GPER1 activation significantly reduced on rat neuronal cells. Aβ1–42 induced cell death was significantly reduced by co-incubating with G-1. Our results suggest that G-1 treatment protects neurons from Aβ1–42 induced neurotoxicity by changing the oxidative parameters on rat neuronal cells.