Aluminium and Neuro-degeneration: Mechanism of Pathogenesis and Possible Strategies for Mitigation

One of the most abundant metal in our environment is aluminium (Al). Occupational exposure of humans to Al takes place during its extractions, processing and fabrications of articles of daily use. Al in drinking water and as well as its use in packaging & storage of food is also a potential source of exposure. Acute exposure of higher concentration or chronic exposure of low concentration of Al leads to its aggregation in various parts of the body, resulting in system toxicity. Brain is highly susceptible to Al accumulation toxicity. In humans, exposure of Al is a risk factor for the starting of Alzheimer Disease. The adverse effect of Al exposure on nervous system results in memory loss, balance problems and impairment of coordination. High level of Al in brain increases lipid peroxidation and oxidative stress and reduces antioxidant enzymes level. It also causes aggregation of amyloid beta proteins and formation of Neurofibrillary Tangles (NFTs) of tau proteins which finally leads to death of neuronal cell and neurotoxicity. Metabolism and excretion of heavy metals including Al is very difficult and its leads to accumulation. The chelation therapy has been proposed where the organic molecules like EDTA, Chlorogenic acid and GSH binds with the heavy metals and facilitates for their excretion from body. However, non-specific binding of these chelators is another major safety concern. Medicinal plants and their phytochemicals with multiple mechanism of action have been proposed as a very good alternative for ameliorating heavy metal induced toxicity. In addition to mild chelating activities, the phytochemicals have antioxidant, anti-inflammatory, cytokine modulatory and other specific actions for proving holistic neuro-protection on heavy metal exposure.