Molecular and Cellular Biochemistry

, Volume 461, Issue 1–2, pp 81–89 | Cite as

SC79, a novel Akt activator, protects dopaminergic neuronal cells from MPP+ and rotenone

  • Jian-liang Zhu
  • Yu-ying Wu
  • Di Wu
  • Wei-Feng Luo
  • Zhi-qing ZhangEmail author
  • Chun-feng LiuEmail author


In pathogenesis of Parkinson’s disease (PD), mitochondrial dysfunction causes substantial reactive oxygen species (ROS) production and oxidative stress, leading to dopaminergic (DA) neuronal cell death. Mitochondrial toxins, including MPP+ (1-methyl-4-phenylpyridinium ion) and rotenone, induce oxidative injury in cultured DA neuronal cells. The current study tested the potential effect of SC79, a first-in-class small-molecule Akt activator, against the process. In SH-SY5Y cells and primary murine DA neurons, SC79 significantly attenuated MPP+- and rotenone-induced viability reduction, cell death, and apoptosis. SC79 activated Akt signaling in DA neuronal cells. Akt inhibition (by LY294002 and MK-2206) or CRISPR-Cas9-mediated Akt1 knockout completely abolished SC79-induced DA neuroprotection against MPP+. Further studies demonstrated that SC79 attenuated MPP+- and rotenone-induced ROS production, mitochondrial depolarization, and lipid peroxidation in SH-SY5Y cells and primary DA neurons. Moreover, upregulation of Nrf2-dependent genes (HO1 and NQO1) and Nrf2 protein stabilization were detected in SC79-treated SH-SY5Y cells and primary DA neurons. Together we show that SC79 protects DA neuronal cells from mitochondrial toxins possibly via activation of Akt-Nrf2 signaling.


Dopaminergic neuronal cells SC79 Akt Parkinson’s disease (PD) Nrf2 


Author contributions

All listed authors designed the study, performed the experiments and the statistical analysis, and wrote the manuscript. All authors have read the manuscript and approved the final version. Author D.W. performed the experiments in the primary neurons.


This work was supported by funds from a special project “diagnostic and therapeutic technology of key clinical diseases” of Suzhou (LCZX201404) and a grant from Suzhou Key Medicine Project Fund of China (Szxk201504) and a grant from National Natural Science Foundation of China (81502162).

Compliance with ethical standards

Conflict of interest

None of the authors have any competing interests.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Emergency and Intensive Care UnitThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
  2. 2.Department of NeurologyThe Second Affiliated Hospital, Institute of Neuroscience, Soochow UniversitySuzhouChina
  3. 3.Institute of Neuroscience, Soochow UniversitySuzhouChina

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