Plant-derived bioactive nutraceuticals mitigate aluminum-mediated neurotoxicity: Elucidated mechanisms and prospects

Aluminum is a stable but highly reactive element and is one of the most abundant elements in the earth crust. Aluminum application is versatile, and remains indispensable across various industries including electronics, construction, automobile, pharmaceuticals, and in advanced technologies. The growing anthropogenic application of aluminum has however raised public health concern, as exposure to aluminum has been linked to neuronal dysfunction and degeneration. Notably, aluminum exposure has been implicated in the pathogenesis of neurodegenerative diseases in humans. Preclinical evidence showed that aluminum exposure can induce disruption of epigenetic mechanisms in the brain, alter neurotransmission dynamics, disrupt neuronal redox homeostasis, cause acute and chronic inflammation, and impair synaptic plasticity in brain cells. Plant-derived bioactive nutraceuticals have been hypothesized to be potential natural therapeutics against aluminum-induced neurotoxicity. In this chapter, we discuss recent in vitro and in vivo studies on the neurotoxic effect of aluminum exposure and its association with neurodegenerative diseases. Moreover, the neuroprotective effects and mechanisms of plant crude extracts, natural diet-derived oils and purified plant-derived bioactive nutraceuticals on neurotoxicity and neurodegenerative diseases induced by aluminum exposure were extensively clarified.