Aluminum Chloride–Driven Neurodegeneration: Interlinking Redox Imbalance, Inflammation Cascade, and Excitotoxic Damage Across Molecular and Behavioral Domains

A common environmental toxin, aluminum chloride (AlCl₃), has been closely linked to the development of neurological and neurodevelopmental diseases. This review incorporates recent research showing how long-term exposure to AlCl₃ impairs the brain's cellular, molecular, and behavioral processes. AlCl₃ causes significant oxidative stress, which is typified by the production of excessive amounts of reactive oxygen species, mitochondrial malfunction, and the activation of apoptotic pathways. Neuronal susceptibility is further exacerbated by parallel neuroinflammatory responses, such as increased pro-inflammatory cytokines, astrocytic and microglial activation, and impaired blood-brain barrier integrity. Glutamate imbalance and NMDA receptor overactivation cause excitotoxicity, which leads to calcium excess and synaptic malfunction. In mouse models, these molecular changes are highly correlated with behavioral impairments such as memory, learning, motor coordination, and exploratory behavior deficiencies. AlCl₃ complex neurotoxic effects are further supported by histopathological observations of neuronal loss, dendritic degeneration, amyloid-beta deposition, and neurofibrillary alterations. Increased cortisol and changed inflammatory markers are examples of systemic disruptions that show toxicity goes beyond the central nervous system. Recent developments in antioxidant, anti-inflammatory, and glutamate-modulating treatment approaches are also highlighted in the review, along with disturbed molecular pathways and new biomarkers related to AlCl₃-induced neurotoxicity. Overall, this synthesis highlights the need for better mechanistic knowledge and efficient treatments to prevent neurodegeneration caused by aluminum.