1. Academic Validation
  2. HLY78 Attenuates Neuronal Apoptosis via the LRP6/GSK3β/β-Catenin Signaling Pathway After Subarachnoid Hemorrhage in Rats

HLY78 Attenuates Neuronal Apoptosis via the LRP6/GSK3β/β-Catenin Signaling Pathway After Subarachnoid Hemorrhage in Rats

  • Neurosci Bull. 2020 Oct;36(10):1171-1181. doi: 10.1007/s12264-020-00532-4.
Xu Luo 1 Lina Li 2 Weilin Xu 3 Yuan Cheng 4 Zongyi Xie 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
  • 2 Department of Nephrology, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 401120, China.
  • 3 Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
  • 4 Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. chengyuan023@aliyun.com.
  • 5 Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China. zyxieneuro2013@yahoo.com.
Abstract

Neuronal Apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage (SAH). Recently, HLY78 has been shown to inhibit Apoptosis in tumor cells and embryonic cells caused by carbon ion radiation through activation of the Wnt/β-catenin pathway. This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH. The results demonstrated that HLY78 attenuated neuronal Apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6 (LRP6), which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta (p-GSK3β) (Ser9), β-catenin, and Bcl-2, accompanied by a decrease of p-β-catenin, Bax, and cleaved Caspase 3. An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78. In conclusion, HLY78 attenuates neuronal Apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats. HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.

Keywords

HLY78; LRP6; Neuronal apoptosis; Subarachnoid hemorrhage.

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