2. Academic Validation
  3. Rotenone-Induced Neurodegeneration Is Enabled by a p38-Parkin-ROS Signaling Feedback Loop

Rotenone-Induced Neurodegeneration Is Enabled by a p38-Parkin-ROS Signaling Feedback Loop

  • J Agric Food Chem. 2021 Nov 24;69(46):13942-13952. doi: 10.1021/acs.jafc.1c04190.
Jialong Chen 1 2,  Mingque Li 1 2,  Xueqiong Zhou 3,  Ailun Xie 1 2,  Ziwei Cai 1 2,  Chunlai Fu 4,  Yongming Peng 1 2,  He Zhang 1 2,  Linhua Liu 1 2
Affiliations

Affiliations

  • 1 Department of Environmental and Occupational Health, School of Public Health, Guangdong Medical University, Dongguan 523808, P. R. China.
  • 2 Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, P. R. China.
  • 3 Department of Occupational Health and Occupational Medicine, School of Public Health, Southern Medical University, Guangzhou 510515, Guangdong, P. R. China.
  • 4 Department of Emergency Intensive Care Unit, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523808, Guangdong, P. R. China.
PMID: 34779196 DOI: 10.1021/acs.jafc.1c04190
Abstract

Rotenone, a component of pesticides, is widely used in agriculture and potentially causes Parkinson's disease (PD). However, the regulatory mechanisms of rotenone-induced PD are unclear. Here, we revealed a novel feedback mechanism of p38-Parkin-ROS regulating rotenone-induced PD. Rotenone treatment led to not only the activation of p38 but also Parkin inactivation and Reactive Oxygen Species (ROS) overproduction in SN4741 cells. Meanwhile, p38 activation regulated Parkin phosphorylation at serine 131 to disrupt Parkin-mediated Mitophagy. Notably, both p38 inhibition and Parkin overexpression decreased ROS levels. Additionally, the ROS inhibitor N-acetyl-l-cysteine (NAC) inhibited p38 and activated Parkin-mediated Mitophagy. Both p38 inhibition and the ROS inhibitor NAC exerted a protective effect by restoring cell death and mitochondrial function in rotenone-induced PD models. Based on these results, the p38-Parkin-ROS signaling pathway is involved in neurodegeneration. This pathway represents a valuable treatment strategy for rotenone-induced PD, and our study provides basic research evidence for the safe use of rotenone in agriculture.

Keywords

Parkin; Parkinson disease; ROS; p38; rotenone.

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