Neurotoxic effects of aluminum and manganese: From molecular to clinical effects

The existing data demonstrate that aluminum (Al) and manganese (Mn) possess neurotoxic effects upon overexposure due to induction of neuronal oxidative stress and apoptosis, synaptic dysfunction and neurotransmitter metabolism, neuroinflammation, and cytoskeletal pathology. However, systematic evidence regarding contribution of these metals to development of neurological diseases are lacking. Therefore, in this review we provide a summary of the existing data on contribution of Al and Mn exposure to brain diseases and its symptoms. Causal relations were demonstrated for development of parkinsonism upon exposure to high doses of Mn, whereas Al overload is considered the key contributor to dialysis encephalopathy. Certain studies demonstrate that Al and Mn overexposure is associated with neurodegenerative diseases including Alzheimer's and Parkinson's diseases, as well as neurodevelopmental disorders like autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Although laboratory studies demonstrate the potential contribution of Al and Mn to molecular pathogenesis of these diseases, clinical findings supporting the causal role of metals is these pathologies are yet insufficient. Therefore, estimation of the contribution of these metals to neurological disorders is essential for development of more effective early diagnostics and prevention of diseases under exposure to adverse neurological effects of Al and Mn compounds. © 2025 Elsevier B.V., All rights reserved.