Targeting Estrogen Signaling in the Radiation-induced Neurodegeneration: A Possible Role of Phytoestrogens

Abstract

Radiation for medical use is a well-established therapeutic method with an excellent prognosis rate for various cancer treatments. Unfortunately, a high dose of radiation therapy comes with its own share of side effects, causing radiation-induced non-specific cellular toxicity; consequently, a large percentage of treated patients suffer from chronic effects during the treatment and even after the post-treatment. Accumulating data evidenced that radiation exposure to the brain can alter the diverse cognitive-related signalings and cause progressive neurodegeneration in patients because of elevated oxidative stress, neuroinflammation, and loss of neurogenesis. Epidemiological studies suggested the beneficial effect of hormonal therapy using estrogen in slowing down the progression of various neuropathologies. Despite its primary function as a sex hormone, estrogen is also renowned for its neuroprotective activity and could manage radiation-induced side-effects as it regulates many hallmarks of neurodegenerations. Thus, treatment with estrogen and estrogen-like molecules or modulators, including phytoestrogens, might be a potential approach capable of neuroprotection in radiation-induced brain degeneration. This review summarized the molecular mechanisms of radiation effects and estrogen signaling in the manifestation of neurodegeneration and highlighted the current evidence on the phytoestrogen mediated protective effect against radiation-induced brain injury. This existing knowledge points towards a new area to expand to identify the possible alternative therapy that can be taken with radiation therapy as adjuvants to improve patients' quality of life with compromised cognitive function.

Estrogen receptor-mediated health benefits of phytochemicals: a review

“…However, the limited bioavailability of natural phytochemicals compared to synthetic drugs is one of the major causes why it is difficult to use them in clinical practice or they fail to be used in clinical treatments. 39 Evidence suggests that when natural compounds are used to target central nervous system disorders, natural products frequently fail to reach sufficient levels in the brain due to their poor bioavailability and blood-brain barrier crossing, resulting in little clinical efficacy. For example, in vitro experiments have indicated that curcumin selectively activates ERβ and affects the upstream factors of the NF-κB signaling pathway, thereby decreasing the expression of β-site amyloid precursor protein-cleaving enzyme 1, making it a potential candidate for Alzheimer's disease (AD) treatment.…”

“…Remarkably, in a recent randomized, double-blind, placebo-controlled clinical research study, an herbal supplement of a mixture of estrogenic substances was demonstrated to exhibit some health benefits in alleviating menopausal conditions including sleep disturbances, depressed mood, irritability, anxiety and a host of other psychiatric-related problems. 39 These results demonstrate the health benefits of phytoestrogens as dietary supplements in clinical trials.…”

Gut Microbiota in Autophagy Regulation: New Therapeutic Perspective in Neurodegeneration

“…As the autophagy pathway is involved in NDDs' causative misfolded protein, a defective autophagy pathway is directly linked to neurodegeneration [69][70][71][72][73][79][80][81][82][83]. In PD, increased alpha-synuclein levels inhibit autophagy by mislocalizing ATG9, a protein with critical functions in autophagosome formation [84].…”

Unveiling the potential anti‐cancer activity of calycosin against multivarious cancers with molecular insights: A promising frontier in cancer research

“…15 Consequently, having such kind of facilities is also widely used for other therapeutic advantages. [16][17][18][19][20] Calycosin, a functional phytoestrogen belonging to the isoflavone category, can be found in the root of Astragalus membranaceus. 21 Calycosin has been traditionally tested in herbal medicine for its myriad of health benefits, including anti-inflammatory, 22 anti-microbial, 23 neuroprotective, 24 and anti-diabetic.…”

“…Because these compounds are safe, less‐toxic, cost‐effective, and readily available sources from villages to cities and underdeveloped to developed countries 15 . Consequently, having such kind of facilities is also widely used for other therapeutic advantages 16‐20 …”