The Mechanism of Acrylamide-Induced Neurotoxicity: Current Status and Future Perspectives

Abstract

Acrylamide (ACR), a potential neurotoxin, is produced by the Maillard reaction between reducing sugars and free amino acids during food processing. Over the past decade, the neurotoxicity of ACR has caused increasing concern, prompting many related studies. This review summarized the relevant literature published in recent years and discussed the exposure to occupational, environmental, and daily ACR contamination in food. Moreover, ACR metabolism and the potential mechanism of ACR-induced neurotoxicity were discussed, with particular focus on the axonal degeneration of the nervous system, nerve cell apoptosis, oxidative stress, inflammatory response, and gut-brain axis homeostasis. Additionally, the limitations of existing knowledge, as well as new perspectives, were examined, specifically regarding the connection between the neurotoxicity caused by ACR and neurodegenerative diseases, NOD-like receptor protein 3 (NLRP3) inflammasome-related neuroinflammation, and microbiota-gut-brain axis signaling. This review might provide systematic information for developing an alternative pathway approach to assess ACR risk.

Ultra-Processed Food Consumption and Depressive Symptoms in a Mediterranean Cohort

“…Finally, the transformation processes of UPFs may lead to the production of substances, such as acrylamide, acrolein, polycyclic aromatic hydrocarbons, and furan that are known to be toxic to the human organism [ 58 ]. These compounds have been shown to potentially exert neurotoxicity via microbiota–gut–brain axis signaling and inflammasome-related neuroinflammation [ 59 , 60 , 61 ].…”

Reactivity of Acrylamides Causes Cytotoxicity and Activates Oxidative Stress Response

“…For the acrylamides tested in this study, the activation of the oxidative stress response via the Nrf-2/Keap-1 pathway was probably triggered by the intracellular formation of ROS as well as a disturbance of the redox balance by the reduction of the intracellular GSH level . This adverse outcome pathway (AOP) has already been shown for different adverse effects, such as hepatotoxicity and neurotoxicity of acrylamides.…”

Pharmacological properties, molecular mechanisms and therapeutic potential of ginsenoside Rg3 as an antioxidant and anti-inflammatory agent

“…When neurons suffer oxidative stress, ROS cooperate with mitochondrial Ca 2+ to increase the permeability of the mitochondrial transition pore (MPTP), resulting in mitochondrial swelling. This process leads to cellular inflammation, senescence, and apoptosis ( Zhao et al, 2022 ). In an H 2 O 2 -induced mitochondrial suspension from the rat forebrain, 20(S)-Rg3 provided neuroprotection and inhibited mitochondrial swelling through suppression of ROS ( Tian et al, 2009 ).…”

“…When neurons are exposed to toxic substances, Rg3 increases peroxidase activity to detoxify and activate PI3K/Akt to prevent apoptosis. The development of neurodegenerative and chronic diseases, including AD, PD, and stroke, is often accompanied by oxidative stress and inflammation ( Zhao et al, 2022 ). These studies suggest that Rg3 inhibits cytokines, COX-2, ROS generation, and mitochondrial dysfunction and enhances peroxidase activity and microglial polarization to exert therapeutic effects on neurological disorders ( Table 3 ).…”

“…Frontiers in Pharmacology frontiersin.org mitochondrial transition pore (MPTP), resulting in mitochondrial swelling. This process leads to cellular inflammation, senescence, and apoptosis (Zhao et al, 2022).…”