{"title":"Unravelling the Mechanistic Approach of Aflatoxin Contaminated Food on Neurodegenerative Diseases-A Novel Approach.","authors":"Ajay Elangovan, Arya Singh, Mahalaxmi Iyer, Sindduja Muthu Kumar, Masako Kinoshita, Jayalakshmi Krishnan, Jyoti Parkash, Neelakshi Verma, Mukesh Kumar Yadav, Arvinder Wander, Dibbanti HariKrishna Reddy, Balachandar Vellingiri","doi":"10.1002/jat.4817","DOIUrl":null,"url":null,"abstract":"<p><p>Aflatoxins (AFs) are a group of toxic secondary metabolites and a dietary toxin produced predominantly by Aspergillus species such as Aspergillus flavus and Aspergillus parasiticus. The four most common and harmful forms of AFs include Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), and Aflatoxin G2 (AFG2), which pose a significant health threat due to their widespread contamination of food and feed products. Particularly, AFB1 has raised a major global health concern. Noxious neurological outcomes have been associated with chronic exposure to AF-contaminated food, contributing to development of neuropathies, demyelinating diseases, and cognitive decline. Disrupted tight junctions of blood-brain barrier (BBB) said to have implicated by AFs toxicity by directly damaging brain endothelial cells. Compromised BBB leads to the formation of DNA adducts, mitochondrial dysfunction, and impaired oxidative phosphorylation, contributing to oxidative stress in neuronal cells. AFs disrupt neuronal signaling pathways by generating reactive oxygen species (ROS) and initiating chronic inflammation, impairing cognitive function and motor control. Mounting evidences suggests that these factors trigger neurological disorders especially neurodegenerative disorders. Neuroprotective compounds, such as hesperetin, N-acetylcysteine (NAC), curcumin, and artichoke extract, have shown promise in counteracting AF-induced neurotoxicity. These compounds could reduce oxidative stress, attenuate inflammation, and support mitochondrial function, offering potential therapeutic strategies to mitigate AF-induced neurodegeneration. This review focuses on the molecular pathways through which AFs exert neurotoxic effects, highlighting their role in the onset of neurodegenerative diseases and potential neuroprotective compounds for therapies have been highlighted.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jat.4817","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aflatoxins (AFs) are a group of toxic secondary metabolites and a dietary toxin produced predominantly by Aspergillus species such as Aspergillus flavus and Aspergillus parasiticus. The four most common and harmful forms of AFs include Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), and Aflatoxin G2 (AFG2), which pose a significant health threat due to their widespread contamination of food and feed products. Particularly, AFB1 has raised a major global health concern. Noxious neurological outcomes have been associated with chronic exposure to AF-contaminated food, contributing to development of neuropathies, demyelinating diseases, and cognitive decline. Disrupted tight junctions of blood-brain barrier (BBB) said to have implicated by AFs toxicity by directly damaging brain endothelial cells. Compromised BBB leads to the formation of DNA adducts, mitochondrial dysfunction, and impaired oxidative phosphorylation, contributing to oxidative stress in neuronal cells. AFs disrupt neuronal signaling pathways by generating reactive oxygen species (ROS) and initiating chronic inflammation, impairing cognitive function and motor control. Mounting evidences suggests that these factors trigger neurological disorders especially neurodegenerative disorders. Neuroprotective compounds, such as hesperetin, N-acetylcysteine (NAC), curcumin, and artichoke extract, have shown promise in counteracting AF-induced neurotoxicity. These compounds could reduce oxidative stress, attenuate inflammation, and support mitochondrial function, offering potential therapeutic strategies to mitigate AF-induced neurodegeneration. This review focuses on the molecular pathways through which AFs exert neurotoxic effects, highlighting their role in the onset of neurodegenerative diseases and potential neuroprotective compounds for therapies have been highlighted.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.