Molecular and Therapeutic Targets of Genistein in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating brain disorder characterized by an increased level of amyloid-beta (Aβ) peptide deposition and neuronal cell death leading to an impairment of learning and thinking skills. The Aβ deposition is a key factor in senile plaques of the AD brain which cause the elevation of intracellular calcium ions and the production of formidable free radicals, both of which greatly contribute to the AD-associated cascade, leading to unstoppable neuronal loss in the hippocampal region of the brain. Natural products are currently considered as an alternative strategy for the discovery of novel multipotent drugs against AD. They include the naturally occurring dietary soy isoflavone genistein which has been recognized to possess several health-promoting effects. Genistein has been mainly focused because of its potential on amelioration of Aβ-induced impairment and its antioxidant capacity to scavenge the free radicals produced in AD. It can also directly interact with the targeted signaling proteins and stabilize their activity to prevent AD. An improved understanding of the direct interactions between genistein and target proteins would contribute to the further development of AD treatment. This review mainly focuses on molecular targets and the therapeutic effects regulated by genistein, which has the ability to directly target the Aβ peptide and to control its activity involved in intracellular signaling pathways, which otherwise would lead to neuronal death in the hippocampal region of the AD brain.