1. Academic Validation
  2. Soybean isoflavones protect dopaminergic neurons from atrazine damage by inhibiting VPS13A to increase autophagy

Soybean isoflavones protect dopaminergic neurons from atrazine damage by inhibiting VPS13A to increase autophagy

  • Ecotoxicol Environ Saf. 2024 Oct 19:286:117225. doi: 10.1016/j.ecoenv.2024.117225.
Peng Li 1 Weiyi Song 1 Nuo Xu 2 Zijie Wang 1 Haoying Pang 3 Dandan Wang 4
Affiliations

Affiliations

  • 1 School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Center for Medical Statistic and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 2 School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 3 First School of Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
  • 4 School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Center for Medical Statistic and Data Analysis, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: lovefamily5@xzhmu.edu.cn.
Abstract

Atrazine (ATR) is a broad-spectrum herbicide with dopaminergic (DAergic) neurotoxicity that can cause Parkinson's disease (PD)-like syndrome. However, research on preventing ATR neurotoxicity is unclear. Soybean Isoflavones (SI) are natural plant compounds with neuroprotective effects. In this study, we found that pre-administration of SI prevented ATR-induced motor dysfunction and substantia nigra pathological damage. RNA-seq datasets revealed that the neuroprotective effect of SI was related to Autophagy. Further experiments showed that ATR inhibited Autophagy, and SI pre-administration before ATR exposure increased Autophagy. In addition, single-cell data analysis combined with experimental verification showed that the gene VPS13A was a key target by which SI protected DAergic neurons from ATR damage, and inhibiting VPS13A-induced Autophagy was a key mechanism enabling SI prevention of neuron damage. Together, these findings provide new insights for the development of preventive measures and intervention targets protecting against functional neuronal damage caused by ATR and other herbicides.

Keywords

Atrazine; Autophagy; Neuroprotection; Soybean isoflavones; VPS13A.

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