From Diet to Brain: Bioactive Nutrients in Estrogen-Related Neuroinflammation

For decades, medical research has predominantly focused on male physiology, leaving female-specific biological features significantly understudied. We are now entering a revolutionary era where the advancement of technology allows us to dive into complex molecular mechanisms, utilizing sophisticated statistical analysis to manage enormous datasets. These developments reveal a critical need to comprehend sex dimorphism in both .physiological and pathological processes Neuroinflammation—a key component in the progression of many neurodegenerative and psychiatric diseases—exhibits significant, sex-dependent differences in prevalence, intensity, and cellular mechanisms. Generally, females show a higher susceptibility to neuroinflammatory-related autoimmune disorders, such as Multiple Sclerosis, and age-related neurodegeneration, specifically Alzheimer’s Disease (AD). Evidence suggests that estrogen performs several vital neuroprotective functions; consequently, the transition through perimenopause and menopause is strongly linked to increased neuroinflammation .due to the sharp decline in 17β-estradiol (E2) production In this review, we synthesize recent studies focusing on the estradiol-microglia axis, shedding light on sex dimorphism and the complex receptor landscape (including ERα, ERβ, and GPER) to provide deeper insight into the aging female brain. Furthermore, we cover emerging research regarding nutritional and synergistic interventions that target specific .biochemical pathways, with particular consideration for the critical "time windows" of efficacy