Unravelling the Mechanistic Approach of Aflatoxin Contaminated Food on Neurodegenerative Diseases-A Novel Approach.

IF 2.7 4区 医学 Q3 TOXICOLOGY
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
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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.

揭示黄曲霉毒素污染食品对神经退行性疾病的作用机制——一种新方法。
黄曲霉毒素(AFs)是一类主要由黄曲霉和寄生曲霉等曲霉种产生的有毒次生代谢物和膳食毒素。四种最常见和最有害的AFs形式包括黄曲霉毒素B1 (AFB1)、黄曲霉毒素B2 (AFB2)、黄曲霉毒素G1 (AFG1)和黄曲霉毒素G2 (AFG2),由于它们广泛污染食品和饲料产品,对健康构成重大威胁。特别是,AFB1引起了一个重大的全球健康问题。有害的神经系统结果与长期暴露于受af污染的食物有关,有助于神经病变、脱髓鞘疾病和认知能力下降的发展。血脑屏障(BBB)紧密连接的破坏被认为与AFs毒性直接损害脑内皮细胞有关。血脑屏障受损会导致DNA加合物的形成、线粒体功能障碍和氧化磷酸化受损,从而导致神经元细胞的氧化应激。AFs通过产生活性氧(ROS)、引发慢性炎症、损害认知功能和运动控制来破坏神经元信号通路。越来越多的证据表明,这些因素会引发神经系统疾病,尤其是神经退行性疾病。神经保护化合物,如橙皮苷、n -乙酰半胱氨酸(NAC)、姜黄素和朝鲜蓟提取物,已显示出对抗af诱导的神经毒性的希望。这些化合物可以减少氧化应激,减轻炎症,支持线粒体功能,为减轻af诱导的神经变性提供了潜在的治疗策略。本文综述了AFs发挥神经毒性作用的分子途径,强调了它们在神经退行性疾病发病中的作用,并强调了潜在的神经保护化合物治疗。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
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.
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