NHRI researcher reports the relationship between ischemia-induced neurodegeneration and PKCε

Global cerebral ischemia resulting from cardiac arrest causes selective neurodegeneration in the hippocampal CA1 region. Protein Kinase C epsilon (PKCε) is a member of the novel PKC subfamily and plays a vital role in ischemic preconditioning. Previous studies have shown that pharmacological activation of PKCε confers neuroprotection. However, the role of endogenous PKCε after cerebral ischemia remains subtle. Dr. Wen-Hai Chou from the Center for Neuropsychiatric Research investigated the molecular and cellular activity of PKCε in disease progression.

The team used male PKCε‐null mice to assess the effects of PKCε deficiency on neurodegeneration after transient global cerebral ischemia, and demonstrated the neuroprotective effects of PKCε deficiency on neurodegeneration after transient global cerebral ischemia, suggesting that reduced mitochondrial translocation of PKCδ may contribute to the neuroprotective action in male PKCε‐null mice.

Apart from that, findings from Dr. Chou’s team suggested that the PKCε–ATF2 signaling pathway is involved in the regulation of neurodegeneration in the hippocampus after cerebral ischemia. They found that PKCε phosphorylates ATF2 at Thr-52 in hippocampal neurons. In response to global cerebral ischemia, the expression of PKCε was gradually reduced, resulting in mitochondrial translocation of ATF2 and neurodegeneration. In addition, the team also characterized the regulatory role of PKCε in nucleocytoplasmic trafficking of ATF2 after global cerebral ischemia.

Citation:

  1. Kumar, V., Weng, Y.-C., Wu, Y.-C., Huang, Y.-T, Liu, T.-H., Kristian, T., Liu, Y.-L., Tsou, H.-H., *Chou, W.-H. (2019) Genetic inhibition of PKCε attenuates neurodegeneration after global cerebral ischemia in male mice. Journal of Neuroscience Research. 97(4):444-455. doi: 10.1002/jnr.24362.
  2. Kumar, V., Weng, Y.-C., Wu, Y.-C., Huang, Y.-T, *Chou, W.-H. (2018) PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration. BMC Neuroscience. 19:76. doi: 10.1186/s12868-018-0479-z.

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