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NGF receptors and PI3K/AKT pathway involved in glucose fluctuation-induced damage to neurons and α-lipoic acid treatment

  • Yan, Ting1
  • Zhang, Zhihui2, 3
  • Li, Danqing4
  • 1 Huai’an Cancer Hospital, Huaian, Jiangsu, China , Huaian (China)
  • 2 Shanghai University of Traditional Chinese Medicine, Shanghai, China , Shanghai (China)
  • 3 Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai, China , Shanghai (China)
  • 4 The Second Hospital Affiliated To Dalian Medical University, Dalian, China , Dalian (China)
Published Article
BMC Neuroscience
Springer (Biomed Central Ltd.)
Publication Date
Sep 17, 2020
DOI: 10.1186/s12868-020-00588-y
Springer Nature


BackgroundGlucose fluctuation promotes neuronal apoptosis, which plays a central role in diabetic encephalopathy (DE). Nerve growth factor (NGF), and its interaction with high-affinity (TrkA) and low-affinity (p75NTR) receptors, are involved in neuronal survival. NGF/TrkA contributes to the activation of the PI3K/AKT pathway, which is beneficial for neuronal survival, and α-Lipoic acid (ALA) exerts clinically favorable neuroprotective effects in the periphery. Whether NGF receptors and the PI3K/AKT pathway are involved in glucose fluctuation-induced neuronal damage, as well as the potential molecular mechanism of ALA in protecting glucose fluctuation-induced neuronal damage, remain unclear.ResultsThe results indicated that constant high glucose (CHG) and intermittent high glucose (IHG) significantly increased the expression of Bax and caspase-3, and decreased the expression of TrkA/p75NTR and p-AKT/AKT, while ALA stimulation reversed the above proteins in PC12 cells. IHG stimulates apoptosis more effectively than CHG in PC12 cells, which is related to the PI3K/AKT pathway but not to the TrkA/p75NTR. Furthermore, neuronal apoptosis induced by IHG was aggravated by the TrkA inhibitor K252a or the PI3K/AKT inhibitor LY294002, but this effect was alleviated by the p75NTR inhibitor TAT-pep5.ConclusionGlucose fluctuation induced cell apoptosis by regulating the TrkA/p75NTR and PI3K/AKT pathway, meanwhile ALA exhibited neuroprotective effects in response to IHG and CHG. These observations indicated that the PI3K/AKT pathway and the balance of TrkA/p75NTR are likely to serve as potential therapeutic targets for DE. In addition, ALA could be a possible therapeutic drug for DE.

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