Mechanistic progression of acrylamide neurotoxicity linked to neurodegeneration and mitigation strategies

Abstract

Acrylamide (AA) is a potential neurotoxic chemical used widely in numerous large-scale industries and molecular research labs. It is a common toxic contaminant in potato and grain-based food products prepared at high temperatures. AA has received serious attention due to the cumulative toxic level exposure to the human population regularly through dietary, environmental, and cosmetics routes other than just occupational exposure. AA is a well-characterized neurotoxin in many rodents and human studies; however mechanistic pathway lacks detailed characterization. Putatively, AA exerts its neurotoxic effects primarily mediated by terminal nerve damage due to inhibition of neurotransmission upon formation of irreversible AA-neuronal protein adducts. Other potential contributors to the AA-induced neuropathological alterations involve an imbalance in redox potential in neuronal cells, inhibition of kinesin-based axonal transport, increased neuronal apoptosis, degenerative changes in cholinergic and dopaminergic neurons, and hyperphosphorylation of Tau. These neurological alterations substantiate the prognosis of the pathological development of severe neurodegenerative diseases. This review summarizes the possible advances in understanding the neuropathological mechanisms of AA-induced neurotoxicity and its clinical implications. Furthermore, we also discuss the potential therapeutic and mitigation strategies to counter the severe toxic health implications of AA.