Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation

  • Authors:
    • Tao Hu
    • Shan‑Shan Li
    • Min‑Nan Lu
    • Li Zhang
    • Bo Chen
    • Rui Mao
    • Rong Mei
    • Ya‑Xin Tan
    • Shan Li
    • Yan‑Bin Xiyang
  • View Affiliations

  • Published online on: June 20, 2019     https://doi.org/10.3892/mmr.2019.10406
  • Pages: 2002-2011
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Abstract

Voltage‑gated sodium channel β2 (Navβ2), as an unconventional substrate of β‑site amyloid precursor protein cleaving enzyme 1, is involved in regulating the neuronal surface expression of sodium channels. A previous study demonstrated that knockdown of Navβ2 protected neurons and induced spatial cognition improvement by partially reducing pathological amyloidogenic processing of amyloid precursor protein (APP) in aged APP/presenilin 1 (PS1) transgenic mice. The present study aimed to investigate whether Navβ2 knockdown altered APP metabolism via regulation of the Aβ‑degrading enzyme neprilysin (NEP). APPswe/PS1ΔE9 mice (APP/PS1 transgenic mice with a C57BL/6J genetic background) carrying a Navβ2‑knockdown mutation (APP/PS1/Navβ2‑kd) or without Navβ2 knockdown (APP/PS1) were used for cell culture and further analysis. The present results demonstrated that in APP/PS1 mouse‑derived neurons, Navβ2 knockdown partially reversed the reduction in pathological APP cleavage, and the recovery of neurite extension and neuron area. Additionally, Navβ2 knockdown increased NEP activity and levels, and the levels of intracellular domain fragment binding to the NEP promoter. The present findings suggested that knockdown of Navβ2 reversed the APP/PS1 mutation‑induced deficiency in amyloid β degradation by regulating NEP.
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August-2019
Volume 20 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Hu T, Li SS, Lu MN, Zhang L, Chen B, Mao R, Mei R, Tan YX, Li S, Xiyang YB, Xiyang YB, et al: Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation. Mol Med Rep 20: 2002-2011, 2019
APA
Hu, T., Li, S., Lu, M., Zhang, L., Chen, B., Mao, R. ... Xiyang, Y. (2019). Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation. Molecular Medicine Reports, 20, 2002-2011. https://doi.org/10.3892/mmr.2019.10406
MLA
Hu, T., Li, S., Lu, M., Zhang, L., Chen, B., Mao, R., Mei, R., Tan, Y., Li, S., Xiyang, Y."Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation". Molecular Medicine Reports 20.2 (2019): 2002-2011.
Chicago
Hu, T., Li, S., Lu, M., Zhang, L., Chen, B., Mao, R., Mei, R., Tan, Y., Li, S., Xiyang, Y."Neuroprotection induced by Navβ2‑knockdown in APP/PS1 transgenic neurons is associated with NEP regulation". Molecular Medicine Reports 20, no. 2 (2019): 2002-2011. https://doi.org/10.3892/mmr.2019.10406