The Possible Association Between Bisphenol A (BPA) and the Neuropathological Processes Characteristic of Alzheimer's Disease-A Systematic Review of the Literature.

Despite decades of control measures, lead (Pb) remains a pervasive environmental toxicant because legacy contamination and ongoing industrial activities continue to sustain human exposure [,,]. Its health burden is particularly evident in the nervous system, where early-life exposure can lead to long-lasting impairments in learning capacity, memory formation, and behavioral regulation []. In China, nationwide blood lead mapping showed that children remain vulnerable to Pb exposure, despite declining blood lead levels []. Even at relatively low levels, Pb exposure may affect the developing brain by entering neural tissue and disturbing neuronal homeostasis, thereby contributing to Pb-induced neurotoxicity []. Pb-induced neurotoxicity is closely associated with cognitive dysfunction and hippocampal injury [,]. Experimental studies have shown that Pb exposure impairs hippocampus-dependent learning and memory, accompanied by neuronal loss and synaptic damage in brain regions involved in cognition [,]. These findings provide a pathological basis for linking Pb exposure to long-term neurological impairment. Mechanistically, Pb-induced neuronal injury is partly related to oxidative stress, as excessive reactive oxygen species (ROS) can weaken endogenous antioxidant defense and disturb neuronal homeostasis [,,]. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of this defensive response, and its dysfunction may increase neuronal susceptibility to toxic stress [,]. Recent evidence further indicates that Pb exposure can promote ferroptosis-related injury by disrupting the solute carrier family 7 member 11/glutathione peroxidase 4 (SLC7A11/GPX4) defense system, thereby connecting oxidative imbalance with regulated neuronal death [,]. Together, these studies suggest that effective intervention should not only reduce behavioral deficits but also preserve neuronal integrity and cellular stress resistance. More broadly, the translation of food-derived bioactive compounds into health-oriented applications has become an expanding area of food and nutrition research []. Experimental studies further indicate that botanical extracts and dietary bioactives can exert antioxidant, immunomodulatory, and neuroprotective effects in neuronal models [,]. As a representative natural product with neuroprotective potential, has received sustained attention for its broad pharmacological activities in the nervous system []. Ginsenosides are the major bioactive saponins of , with representative monomers such as Rb1, Rd, Re, Rg1, and Rg3 showing neuroprotective potential in experimental models of neural injury [,]. Recent evidence also indicates that ginsenosides can attenuate neuroinflammatory responses in experimental models of neurological dysfunction []. Among these compounds, ginsenoside Rg1 is one of the most extensively studied monomers and has attracted particular interest in neurological disease research [,]. Modern phytochemical and pharmacological studies have demonstrated that Rg1 exhibits prominent neuroprotective, anti-inflammatory, and antioxidant properties []. Rg1 has been shown to activate the Nrf2/HO-1 antioxidant axis, reduce ROS generation and neuronal apoptosis in models of cerebral ischemia–reperfusion injury [,]. In addition, Rg1 prevents oxidative stress-induced hippocampal neuronal apoptosis via activation of Nrf2/ARE signaling and upregulation of downstream antioxidant enzymes []. Although Rg1 can regulate Nrf2 signaling in several models of neural injury, its protective role under Pb exposure remains insufficiently defined. It is also unclear whether Rg1 links Nrf2-mediated antioxidant defense to ferroptosis inhibition in Pb-induced neurotoxicity. Direct pathway-specific evidence for this relationship is still lacking.