Pesticides Exposure-Induced Changes in Brain Metabolome: Implications in the Pathogenesis of Neurodegenerative Disorders

Abstract

Pesticides have been used in agriculture, public health programs, and pharmaceuticals for many decades. Though pesticides primarily target pests by affecting their nervous system and causing other lethal effects, these chemical entities also exert toxic effects in inadvertently exposed humans through inhalation or ingestion. Mounting pieces of evidence from cellular, animal, and clinical studies indicate that pesticide-exposed models display metabolite alterations of pathways involved in neurodegenerative diseases. Hence, identifying common key metabolites/metabolic pathways between pesticide-induced metabolic reprogramming and neurodegenerative diseases is necessary to understand the etiology of pesticides in the rise of neurodegenerative disorders. The present review provides an overview of specific metabolic pathways, including tryptophan metabolism, glutathione metabolism, dopamine metabolism, energy metabolism, mitochondrial dysfunction, fatty acids, and lipid metabolism that are specifically altered in response to pesticides. Furthermore, we discuss how these metabolite alterations are linked to the pathogenesis of neurodegenerative diseases and to identify novel biomarkers for targeted therapeutic approaches.

Keywords: Brain; Metabolites; Neurodegenerative disorders; Neurotoxicity; Organophosphate; Pesticides.

Fig. 1

Flowchart depicting the literature search strategy for the review

Fig. 2

Alterations in quinolinic acid and kynurenic acid levels due to pesticide exposure

Fig. 3

Alterations in the glutathione and glutathione S-transferase levels due to pesticide exposure

Fig. 4

Changes in different metabolite levels involved in dopamine metabolism due to pesticide exposure