Molecular, Biochemical, and Epigenetic Mechanisms Involved in Environmental Neurotoxicants Exposure Induced Premature Brain Aging with Central Focus on Pesticides Role.

Abstract

Environmental neurotoxicants are widely used in various industries, including agriculture and public health sectors, and are known to cause harmful effects to humans through environmental and occupational exposures. Neurotoxicants are increasingly recognized as significant contributors to premature brain aging and neurodegenerative disorders. This review delineates the literature on neurotoxicant-induced comprehensive biochemical and molecular pathways leading to brain aging by consolidating the mechanistic insights with a main focus on pesticides. Exposome research combines environmental monitoring with integrative multiomics technologies such as exposomics, proteomics, and adductomics to map the real impact of neurotoxicants in neurodegenerative disorders. We discussed the intersecting molecular genetic pathways, including genomic instability, telomere attrition, epigenetic remodeling, including aberrant DNA methylation and microRNA deregulation, and biochemical pathways, including mitochondrial dysfunction, oxidative stress, impaired proteostasis, and autophagic disruption across the lifespan. These complex and often intergenerational mechanisms can be contextualized within the exposome framework to emphasize the cumulative environmental exposures that shape premature brain aging. Neurotoxicant exposure interferes with critical neuroprotective pathways, induces systemic metabolic dysregulation, neuroinflammation, and neurodegeneration, and disturbs the gut-brain axis, further amplifying neuronal vulnerability. A mechanistic understanding is important for toxicity screening and regulatory frameworks to mitigate the long-term consequences of neurotoxic insults. This review highlights the importance of eco-friendly alternatives such as integrated pest management strategies to reduce pesticide burdens on humans and environmental health for sustainable development.