> Details

Wan, Fang [Author]; Yu, Ting [Author]; Hu, Junjie [Author]; Yin, Sijia [Author]; Li, Yunna [Author]; Kou, Liang [Author]; Chi, Xiaosa [Author]; Wu, Jiawei [Author]; Sun, Yadi [Author]; Zhou, Qiulu [Author]; Zou, Wenkai [Author]; Zhang, Zhentao [Author]; Wang, Tao [Author]

The Pyrethroids Metabolite 3-Phenoxybenzoic Acid Induces Dopaminergic Degeneration

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Book
  • Title: The Pyrethroids Metabolite 3-Phenoxybenzoic Acid Induces Dopaminergic Degeneration
  • Contributor: Wan, Fang [Author]; Yu, Ting [Author]; Hu, Junjie [Author]; Yin, Sijia [Author]; Li, Yunna [Author]; Kou, Liang [Author]; Chi, Xiaosa [Author]; Wu, Jiawei [Author]; Sun, Yadi [Author]; Zhou, Qiulu [Author]; Zou, Wenkai [Author]; Zhang, Zhentao [Author]; Wang, Tao [Author]
  • Published: [S.l.]: SSRN, [2022]
  • Extent: 1 Online-Ressource (38 p)
  • Language: English
  • DOI: 10.2139/ssrn.4032237
  • Identifier:
  • Origination:
  • Footnote:
  • Description: Exposure to pyrethroids, a significant class of the most widely used agricultural chemicals, has been associated with an increased risk of Parkinson’s disease (PD). However, the underlying mechanisms of pyrethroid-induced Parkinsonism remain unknown. In this study, we focused on 3-phenoxybenzoic acid (3-PBA), a common and prominent metabolite of most pyrethroids produced via hydrolysis by carboxylesterases (CEs) in mammals. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and observed the accumulation of 3-PBA in mouse brain tissues over time following exposure to pyrethroids. By quantifying the binding of 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) to the dopamine transporter (DAT) using positron emission tomography (PET), we observed that different concentrations of 3-PBA induced different variations in DAT levels in vivo, and confirmed that DAT might be a gateway for 3-PBA in dopaminergic cells. By elucidating the relationship between 3-PBA and neurodegeneration in a 3-PBA-treated mouse model, we revealed that the lysosomal protease asparagine endopeptidase (AEP) could cleave human α-synuclein (α-syn), thereby inducing its aggregation, escalating its neurotoxicity, and leading to dopaminergic neuronal loss, decreased tyrosine hydroxylase (TH) levels, and motor impairments. Overall, these findings support that 3-PBA exposure could mimic the pathological and pathogenetic features of PD, showing that this metabolite is a key pathopoiesis compound in pyrethroid-related etiopathological effects and a possible dopamine neurotoxin. Although this metabolite is easily accumulated, it is an often ignored environmental risk factor for PD
  • Access State: Open Access