Effect of Aflatoxin B1 on the Nervous System: A Systematic Review and Network Analysis Highlighting Alzheimer's...

Exposure to aflatoxin (AF) triggers the production of inflammatory molecules and free radicals, leading to chronic inflammation, cancer, and neurodegenerative diseases. This systematic review evaluated the effects of AFB1 on the nervous system, particularly focusing on Alzheimer's disease (AD). A comprehensive search was conducted in Scopus, Cochrane Library, PubMed, and Web of Science databases up to 1 June 2024, without restrictions. From 993 records retrieved, 16 articles were included in the systematic review. AFB1 participates in various biochemical processes and pathological conditions. The study highlights that AFB1 contributes to AD by inducing DNA damage, oxidative stress, and endoplasmic reticulum (ER) stress, impairing DNA repair mechanisms. This results in neuronal damage, cognitive decline, and neurodegeneration. AFB1 also affects key signaling pathways, reduces sodium-potassium pump activity, and disrupts cell cycle regulation involving p53, leading to neurotoxicity, inflammation, and the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles. Additionally, network analysis revealed 309 genes associated with AD, inflammation, angiopathy, and aflatoxin B1 (AFB1). Among these, ESR1 exhibited the highest number of direct connections to other nodes within the network. The gene TP53 played a pivotal role in mediating communication among genes, while the EP300 gene significantly influenced the overall network structure. Additionally, KEGG enrichment analysis demonstrated that these 309 genes are substantially involved in pathways related to cancer, the FoxO signaling pathway, apoptosis, and AD. In summary, the study highlights that AFB1 causes DNA damage and stress, leading to cognitive decline and neurodegeneration. It disrupts signaling pathways, damages neurons, and affects DNA repair, contributing to neurotoxicity and inflammation. PROSPERO registration number: CRD420250651007.