Unveiling the crosslinks between pesticide exposure and the development of neurodegenerative disorders

Pesticides are ubiquitous in the environment, contaminating atmospheric air, water, and soil. Moreover, pesticide residues have also been reported in foods, which could act as a potent source to human exposure. Pesticides can persist in the environment from days to months. Humans are mainly exposed to these detrimental compounds through nasal, oral, and dermal routes. Pesticide residues and their metabolites can accumulate in various organs, including the organs of central nervous system. The blood-brain barrier prevents xenobiotics from entering the brain tissues. However, some pesticides can disrupt the blood-brain barrier and invade the central nervous system. Pesticides disturb the redox homeostasis in neural cells, affecting the structural and functional integrity of crucial proteins and lipids of biological significance. In addition, neuroinflammation is another mechanism through which pesticides can injure the neurons, causing permanent damage to the central nervous system and triggering the development of neurodegenerative diseases. Pesticide-induced loss of dopaminergic neurons in the substantia nigra compacta region of the brain affects motor activity. Besides aggregation of misfolded alpha-synuclein, hyperphosphorylation of tau, and dysregulated calcium homeostasis are also evident in animal models following pesticide exposure. Continued activation of microglia and astrocytes following pesticide exposure can further escalate the adverse effects. Therefore, pesticides pose serious threats to the human nervous system. This review presents the various sources of pesticide exposure for humans and their impacts on the central nervous system. This review also comprehensively discusses the latest available studies on potential mechanisms through which pesticides can damage the central nervous system and trigger neurodegeneration.