The Impact of Estrogen and Estrogen-Like Molecules in Neurogenesis and Neurodegeneration: Beneficial or Harmful?

Abstract

Estrogens and estrogen-like molecules can modify the biology of several cell types. Estrogen receptors alpha (ERα) and beta (ERβ) belong to the so-called classical family of estrogen receptors, while the G protein-coupled estrogen receptor 1 (GPER-1) represents a non-classical estrogen receptor mainly located in the plasma membrane. As estrogen receptors are ubiquitously distributed, they can modulate cell proliferation, differentiation, and survival in several tissues and organs, including the central nervous system (CNS). Estrogens can exert neuroprotective roles by acting as anti-oxidants, promoting DNA repair, inducing the expression of growth factors, and modulating cerebral blood flow. Additionally, estrogen-dependent signaling pathways are involved in regulating the balance between proliferation and differentiation of neural stem/progenitor cells (NSPCs), thus influencing neurogenic processes. Since several estrogen-based therapies are used nowadays and estrogen-like molecules, including phytoestrogens and xenoestrogens, are omnipresent in our environment, estrogen-dependent changes in cell biology and tissue homeostasis have gained attention in human health and disease. This article provides a comprehensive literature review on the current knowledge of estrogen and estrogen-like molecules and their impact on cell survival and neurodegeneration, as well as their role in NSPCs proliferation/differentiation balance and neurogenesis.

Estrogenic Plants: to Prevent Neurodegeneration and Memory Loss and Other Symptoms in Women After Menopause

“…Recently encouraging clinical results with a combination of herbs have shown to be effective and safe in decreasing menopause symptoms (Rattanatantikul et al, 2020). Also, phytoestrogens and their metabolites from medicinal plants have been shown to mimic the benefits of endogenous estrogens, and estrogen-based therapies are considered promising approaches for preventing the onset and progression of neurodegenerative disorders (Bustamante-Barrientos et al, 2021). Though, xenoestrogens derived from plastic polycarbonates, such as water bottles and varnish coating in food cans, can alter estrogen-mediated signaling pathways inducing a negative effect on health.…”

Discovery of 8-prenylnaringenin from hop (Humulus lupulusL.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer's disease

“…88,89 It has been reported that estradiol boosts neurogenesis correlating with cognitive improvement. 90,91 Moreover, estradiol can also ameliorate the neurodegenerative processes of Alzheimer's and Parkinson's diseases. 91,92 It is noteworthy that the phytoestrogen 8-PN, with estradiol-like effects, exhibits an exceptional activity in binding to the a-estrogen receptor.…”

“…90,91 Moreover, estradiol can also ameliorate the neurodegenerative processes of Alzheimer's and Parkinson's diseases. 91,92 It is noteworthy that the phytoestrogen 8-PN, with estradiol-like effects, exhibits an exceptional activity in binding to the a-estrogen receptor. 93 As well, 8-PN was reported to positively control GABA-induced responses and its potential in neurodifferentiating has also been reported.…”

Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits

“…The health properties of phytoestrogens seem to go beyond their estrogen-like activity. Many studies have demonstrated that they, acting on other target molecules and signaling pathways, exert several health effects such as antiandrogenic properties, antioxidant action, cell cycle and differentiation inhibition, antiangiogenic properties, and modulation of the activity or expression of steroidogenic enzymes [310] The antioxidant activity of genistein in in vitro and in vivo studies has been widely demonstrated. The results of clinical studies on genistein antioxidant activity evaluation have been clear, suggesting that this antioxidant activity could be the most reliable effect of this phytoestrogen.…”