Cellular and molecular events leading to paraquat-induced apoptosis: mechanistic insights into Parkinson’s disease pathophysiology

Wesley Zhi Chung See, Rakesh Naidu, Kim San Tang

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal features of tremor, bradykinesia, rigidity, and postural instability, in addition to other non-motor symptoms. Pathologically, PD is attributed to the loss of dopaminergic neurons in the substantia nigra pars compacta, with the hallmark of the presence of intracellular protein aggregates of α-synuclein in the form of Lewy bodies. The pathogenesis of PD is still yet to be fully elucidated due to the multifactorial nature of the disease. However, a myriad of studies has indicated several intracellular events in triggering apoptotic neuronal cell death in PD. These include oxidative stress, mitochondria dysfunction, endoplasmic reticulum stress, alteration in dopamine catabolism, inactivation of tyrosine hydroxylase, and decreased levels of neurotrophic factors. Laboratory studies using the herbicide paraquat in different in vitro and in vivo models have demonstrated the induction of many PD pathological features. The selective neurotoxicity induced by paraquat has brought a new dawn in our perspectives about the pathophysiology of PD. Epidemiological data have suggested an increased risk of developing PD in the human population exposed to paraquat for a long term. This model has opened new frontiers in the quest for new therapeutic targets for PD. The purpose of this review is to synthesize the relationship between the exposure of paraquat and the pathogenesis of PD in in vitro and in vivo models.

Original languageEnglish
Pages (from-to)3353-3369
Number of pages17
JournalMolecular Neurobiology
Volume59
Issue number6
DOIs
Publication statusPublished - Jun 2022

Keywords

  • Alpha-synuclein
  • Apoptosis
  • Brain-derived neurotrophic factor
  • Endoplasmic reticulum stress
  • Nitrosative stress, Oxidative stress
  • Paraquat
  • Parkinson disease

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