Acrylamide Neurotoxicity as a Possible Factor Responsible for Inflammation in the Cholinergic Nervous System

Int J Mol Sci. 2022 Feb 12;23(4):2030. doi: 10.3390/ijms23042030.


Acrylamide (ACR) is a chemical compound that exhibits neurotoxic and genotoxic effects. It causes neurological symptoms such as tremors, general weakness, numbness, tingling in the limbs or ataxia. Numerous scientific studies show the effect of ACR on nerve endings and its close connection with the cholinergic system. The cholinergic system is part of the autonomic nervous system that regulates higher cortical functions related to memory, learning, concentration and attention. Within the cholinergic system, there are cholinergic neurons, anatomical cholinergic structures, the neurotransmitter acetylcholine (ACh) and cholinergic receptors. Some scientific reports suggest a negative effect of ACR on the cholinergic system and inflammatory reactions within the body. The aim of the study was to review the current state of knowledge on the influence of acrylamide on the cholinergic system and to evaluate its possible effect on inflammatory processes. The cholinergic anti-inflammatory pathway (CAP) is a neuroimmunomodulatory pathway that is located in the blood and mucous membranes. The role of CAP is to stop the inflammatory response in the appropriate moment. It prevents the synthesis and the release of pro-inflammatory cytokines and ultimately regulates the local and systemic immune response. The cellular molecular mechanism for inhibiting cytokine synthesis is attributed to acetylcholine (ACh), the major vagal neurotransmitter, and the α7 nicotinic receptor (α7nAChR) subunit is a key receptor for the cholinergic anti-inflammatory pathway. The combination of ACh with α7nAChR results in inhibition of the synthesis and release of pro-inflammatory cytokines. The blood AChE is able to terminate the stimulation of the cholinergic anti-inflammatory pathway due to splitting ACh. Accordingly, cytokine production is essential for pathogen protection and tissue repair, but over-release of cytokines can lead to systemic inflammation, organ failure, and death. Inflammatory responses are precisely regulated to effectively protect against harmful stimuli. The central nervous system dynamically interacts with the immune system, modulating inflammation through the humoral and nervous pathways. The stress-induced rise in acetylcholine (ACh) level acts to ease the inflammatory response and restore homeostasis. This signaling process ends when ACh is hydrolyzed by acetylcholinesterase (AChE). There are many scientific reports indicating the harmful effects of ACR on AChE. Most of them indicate that ACR reduces the concentration and activity of AChE. Due to the neurotoxic effect of acrylamide, which is related to the disturbance of the secretion of neurotransmitters, and its influence on the disturbance of acetylcholinesterase activity, it can be concluded that it disturbs the normal inflammatory response.

Keywords: acrylamide; cholinergic nervous system; inflammatory response.

Publication types

  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase / metabolism
  • Acrylamide / toxicity*
  • Animals
  • Cholinergic Neurons / drug effects*
  • Cholinergic Neurons / metabolism
  • Cholinergic Neurons / physiology
  • Humans
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism*
  • Receptors, Cholinergic / metabolism


  • Receptors, Cholinergic
  • Acrylamide
  • Acetylcholinesterase
  • Acetylcholine