1. Academic Validation
  2. Surfeit Locus Protein 4 as a Novel Target for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury

Surfeit Locus Protein 4 as a Novel Target for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury

  • Mol Neurobiol. 2023 Oct 16. doi: 10.1007/s12035-023-03687-z.
Wenjie Hu 1 2 Xiangyi Kong 1 Yu Cui 1 Hui Wang 1 Jingchen Gao 1 Xiyuran Wang 1 Shujun Chen 1 Xiaohua Li 1 Shifang Li 1 Fengyuan Che 3 Qi Wan 4 5
Affiliations

Affiliations

  • 1 Institute of Neuroregeneration & Neurorehabilitation, Department of Neurosurgery, School of Basic Medicine, Qingdao University, 308 Ningxia Street, Qingdao, China.
  • 2 Department of Biological Science, Jining Medical University, Rizhao, China.
  • 3 Central Laboratory, Department of Neurology, Linyi People's Hospital, 27 East Jiefang Road, Linyi, China. che1971@126.com.
  • 4 Institute of Neuroregeneration & Neurorehabilitation, Department of Neurosurgery, School of Basic Medicine, Qingdao University, 308 Ningxia Street, Qingdao, China. qiwan1@hotmail.com.
  • 5 Qingdao Gui-Hong Intelligent Medical Technology Co. Ltd, Qingdao High-tech Industrial Development District, 7 Fenglong Road, Qingdao, China. qiwan1@hotmail.com.
Abstract

Surfeit locus protein 4 (SURF4) functions as a cargo receptor that is capable of transporting newly formed proteins from the lumen of the endoplasmic reticulum into vesicles and Golgi bodies. However, the role of SURF4 in the central nervous system remains unclear. The aim of this study is to investigate the role of SURF4 and its underlying mechanisms in cerebral ischemia/reperfusion (I/R) injury in rats, and whether it can be used effectively for novel therapeutic intervention. We also examined whether transcranial direct-current stimulation (tDCS) can exert a neuroprotective effect via SURF4-dependent signalling. Following cerebral I/R injury in rats, a significant increase was observed in the expression of SURF4. In both I/R injury and oxygen-glucose deprivation (OGD) insult, suppressing the expression of SURF4 demonstrated a neuroprotective effect, while overexpression of SURF4 resulted in increased neuronal death. We further showed that the levels of nerve growth factor precursor (proNGF), p75 neurotrophin receptor (p75NTR), sortilin, and PTEN were increased following cerebral I/R injury, and that SURF4 acted through the PTEN/proNGF signal pathway to regulate neuronal viability. We demonstrated that tDCS treatment reduced SURF4 expression and decreased the infarct volume after cerebral I/R injury. Together, this study indicates that SURF4 plays a critical role in ischemic neuronal injury and may serve as a molecular target for the development of therapeutic strategies in acute ischemic stroke.

Keywords

Ischemia/Reperfusion injury; Neuroprotection; SURF4; proNGF; tDCS.

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