Frontiers in Aging Neuroscience (Oct 2021)

Curcumin Reduced H2O2- and G2385R-LRRK2-Induced Neurodegeneration

  • Jinru Zhang,
  • Jinru Zhang,
  • Kai Li,
  • Xiaobo Wang,
  • Xiaobo Wang,
  • Amber M. Smith,
  • Bo Ning,
  • Zhaohui Liu,
  • Chunfeng Liu,
  • Chunfeng Liu,
  • Christopher A. Ross,
  • Wanli W. Smith

DOI
https://doi.org/10.3389/fnagi.2021.754956
Journal volume & issue
Vol. 13

Abstract

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Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are the most frequent genetic factors contributing to Parkinson's disease (PD). G2385R-LRRK2 increases the risk for PD susceptibility in the Chinese population. However, the pathological role of G2385R-LRRK2 is not clear. In this study, we investigate the roles of G2385R-LRRK2 in neurodegeneration underlying PD pathogenesis using cell biology and pharmacology approaches. We demonstrated that expression of G2385R-LRRK2-induced neurotoxicity in human neuroblastoma SH-SY5Y and mouse primary neurons. G2385R-LRRK2 increased mitochondrial ROS, activates caspase-3/7, and increased PARP cleavage, resulting in neurotoxicity. Treatment with curcumin (an antioxidant) significantly protected against G2385R-LRRK2-induced neurodegeneration by reducing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage. We also found that the cellular environmental stressor, H2O2 significantly promotes both WT-LRRK2- and G2385R-LRRK2-induced neurotoxicity by increasing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage, while curcumin attenuated this combined neurotoxicity. These findings not only provide a novel understanding of G2385R roles in neurodegeneration and environment interaction but also provide a pharmacological approach for intervention for G2385R-LRRK2-linked PD.

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