Revisiting the Paraquat-Induced Sporadic Parkinson’s Disease-Like Model

Abstract

Parkinson's disease (PD) is a major neurodegenerative disorder that affects 1-2% of the total global population. Despite its high prevalence and publication of several studies focused on understanding its pathology, an effective treatment that stops and/or reverses the damage to dopaminergic neurons is unavailable. Similar to other neurodegenerative disorders, PD etiology may be linked to several factors, including genetic susceptibility and environmental elements. Regarding environmental factors, several neurotoxic pollutants, including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), have been identified. Moreover, some pesticides/herbicides, such as rotenone, paraquat (PQ), maneb (MB), and mancozeb (MZ), cause neurotoxicity and induce a PD-like pathology. Based on these findings, several in vitro and in vivo PD-like models have been developed to understand the pathophysiology of PD and evaluate different therapeutic strategies to fight dopaminergic neurodegeneration. 6-OHDA and MPTP are common models used in PD research, and pesticide-based approaches have become secondary models of study. However, some herbicides, such as PQ, are commonly used by farming laborers in developing countries. Thus, the present review summarizes the relevant scientific background regarding the use and effects of chronic exposure to PQ in the context of PD. Similarly, we discuss the relevance of PD-like models developed using this agrochemical compound.

NEAT1 is overexpressed in Parkinson's disease substantia nigra and confers drug‐inducible neuroprotection from oxidative stress

“…Because oxidative stress is of high relevance for PD (35), we further tested for NEAT1 elevation in conditions of oxidative stress. For that purpose, we exposed 2 cell lines to the herbicide PQ, known to trigger oxidative stress and PD-related pathways (9). We found robust up-regulation of NEAT1 RNA upon PQ exposure in both the embryonic kidney cell line HEK-293T and the human-derived neuroblastoma cell line SH-SY5Y.…”

“…Autosomal dominant or recessive mutations in several genes have been identified as being involved in familial PD (3), including α-synuclein (4) and the leucine-rich repeat kinase 2 (LRRK2) (5), a PD-associated mutation of which is prevalent in Ashkenazi Jews (6). Other risk factors associated with increased PD prevalence include certain genetic loci (7), male sex (8), and environmental exposure to oxidative stress–inducing toxins (9) such as the herbicide paraquat (PQ) and the fungicide maneb (10). Nevertheless, current therapeutics, as well as most efforts toward development of novel preventive and therapeutic measurements, are similar and indiscriminative for all patients with PD.…”

Role of Lipid Peroxidation Process in Neurodegenerative Disorders

“…Symptomatically, it affects the motor neuron and produces the abnormalities of body movements. The LPO process induces the primary form of sporadic type of Parkinson disease (PD) [66]. Mainly, dopaminergic neuron damage occurs in the substantia nigra, locus ceruleus, dorsal motor nucleus and substantia innominata [67].…”

A lncRNA survey finds increases in neuroprotective LINC‐PINT in Parkinson’s disease substantia nigra

“…While PD is largely considered a sporadic disease, autosomal dominant or recessive mutations in several genes including alpha‐synuclein (SNCA) have been identified as inducing familial PD (Hauser & Hastings, ). Another risk factor associated with increased PD prevalence is environmental exposure to toxins such as the oxidative stress‐inducing herbicide Paraquat (PQ) (Bastias‐Candia, Zolezzi, & Inestrosa, ). However, the contributions to PD of changes in the brain's transcriptome are incompletely understood.…”