2. Academic Validation
  3. Protection of neuronal cells from excitotoxicity by disrupting nNOS-PSD95 interaction with a small molecule SCR-4026

Protection of neuronal cells from excitotoxicity by disrupting nNOS-PSD95 interaction with a small molecule SCR-4026

  • Brain Res. 2016 Oct 1;1648(Pt A):250-256. doi: 10.1016/j.brainres.2016.07.012.
Shi-Fu Mo 1,  Gao-Yong Liao 2,  Jie Yang 2,  Meng-Yu Wang 2,  Yang Hu 2,  Guo-Ning Lian 2,  Ling-Dong Kong 3,  Yong Zhao 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu 210023, PR China; MtC BioPharma Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China; Simcere Pharmaceutical Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China.
  • 2 MtC BioPharma Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China; Simcere Pharmaceutical Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, Jiangsu 210023, PR China. Electronic address: kongld@nju.edu.cn.
  • 4 MtC BioPharma Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China; Simcere Pharmaceutical Co., Ltd, 699-18 Xuanwu Avenue, Nanjing, Jiangsu 210042, PR China. Electronic address: zhaoyong@mtcbiopharma.com.
PMID: 27421179 DOI: 10.1016/j.brainres.2016.07.012
Abstract

Stroke is a major public health problem leading to high rates of death and disability in adults. Coupling of postsynaptic density protein-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) plays an important part in neuronal damage caused by stroke. Recent studies suggest the possibility of alleviating post ischemia neuron damage by blocking ischemia-induced nNOS-PSD-95 association. Here, we report a small-molecular inhibitor of nNOS-PSD-95 interaction, SCR-4026, which exhibits neuroprotective activities in NMDA-induced or Oxygen and glucose deprivation (OGD)-induced neuronal damage in primary cortical neurons cultures, and ameliorated focal cerebral ischemic damage in rats subjected to middle cerebral artery occlusion (MCAO) and reperfusion. Furthermore, we found that SCR-4026 was also able to promote neural stem cells to differentiate into neurons-like cells, which is potentially of great significance for neural protection. Taken together, SCR-4026 is identified as a novel small molecule that shows great potential in treating stroke.

Keywords

Cerebral ischemia; PSD95; nNOS.

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