Anti-amnesic and Neuroprotective Potential of Genistein Against Alzheimer's Disease

Alzheimer's disease, the most prevalent neurodegenerative disorder, is characterized by language deficits, impairment of problem-solving ability, loss of learning abilities, and cognitive dysfunction. Progression of Alzheimer's disease involves multifactorial pathogenesis including cholinergic and mitochondrial dysfunction, oxidative stress burden, calcium homeostasis imbalance, accumulation of amyloid beta protein, and Tau protein as neurofibrillary tangles in the brain. Natural products especially flavonoids are currently thought of as alternative plant molecules for finding new and robust drugs for the remedy of this disease. Recently, dietary flavonoids have drawn more attention from researchers as novel candidates for the management of neurodegenerative disorders including Alzheimer's disease. The phytoestrogen genistein (4,5,7-trihydroxyisoflavone) is a naturally occurring isoflavone which is an important nutraceutical molecule found in plants, including soybean and fava beans with a multitude of health benefits. The neuroprotective effect of genistein is primarily mediated by its antioxidative properties. Parallel to antioxidant activity, genistein exhibits numerous pharmacological effects against Alzheimer's disease-like manifestation including the improvement of spatial memory and learning; prevents amyloid beta accumulation, suppression of mitochondrial damage, and inhibition of inflammatory mediators; reduces caspase-3 overexpression, and upregulation of protein kinase C and nuclear factor erythroid 2-related factor 2/heme oxygenase-1/phosphoinositide 3-kinase signaling pathway in experimental conditions. This review offers revealing insights into numerous possible molecular mechanisms of genistein for the management of Alzheimer's disease based on neurobiological studies and proposes an alternate pharmacotherapy for the management of Alzheimer's disease. Additional research is required to evaluate the efficacy and underlying mechanism of genistein as a novel pharmacophore for the management of Alzheimer's disease-like manifestation.