The susceptibility of humans to neurodegenerative and neurodevelopmental toxicities caused by organophosphorus pesticides

• Published in: Archives of toxicology 2023-12, Vol.97 (12), p.3037-3060
• Main Authors: Mostafalou, Sara, Abdollahi, Mohammad
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Apolipoprotein E; Apoptosis; Attention deficit hyperactivity disorder; Autism; Autophagy; Biomedical and Life Sciences; Biomedicine; Cholinergics; Cholinesterase; Dopamine D4 receptors; Dopamine receptors; Environmental Health; Gene polymorphism; Genetic diversity; Glutamatergic transmission; Intellectual disabilities; Movement disorders; Neurodegenerative diseases; Neurodevelopmental disorders; Neurological diseases; Neurological disorders; Neurotoxicity; Nitric-oxide synthase; Occupational Medicine/Industrial Medicine; Organophosphorus pesticides; Oxidative stress; Parkinson's disease; Pesticide toxicity; Pesticides; Pharmacology/Toxicology; Review Article; Synapses; Toxicology; γ-Aminobutyric acid
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-023-03604-2

The toxicology field is concerned with the impact of organophosphorus (OP) compounds on human health. These compounds have been linked to an increased risk of neurological disorders, including neurodegenerative and neurodevelopmental diseases. This article aims to review studies on the role of OP compounds in developing these neurological disorders and explore how genetic variations can affect susceptibility to the neurotoxicity of these pesticides. Studies have shown that exposure to OP compounds can lead to the development of various neurological disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), attention deficit hyperactivity disorder (ADHD), autism, intellectual disability, and other developmental neurotoxicities. Apart from inhibiting the cholinesterase enzyme, OP compounds are believed to cause other pathological mechanisms at both the extracellular level (cholinergic, serotonergic, dopaminergic, glutamatergic, and GABAergic synapses) and the intracellular level (oxidative stress, mitochondrial dysfunction, inflammation, autophagy, and apoptosis) that contribute to these disorders. Specific genetic polymorphisms, including PON1, ABCB1, NOS, DRD4, GST, CYP, and APOE, have increased the risk of developing OP-related neurological disorders.