2. Academic Validation
  3. Lysine-specific demethylase 1 inhibition enhances autophagy and attenuates early-stage post-spinal cord injury apoptosis

Lysine-specific demethylase 1 inhibition enhances autophagy and attenuates early-stage post-spinal cord injury apoptosis

  • Cell Death Discov. 2021 Apr 6;7(1):69. doi: 10.1038/s41420-021-00455-7.
Yang Gu  # 1,  Dehui Chen  # 1,  Linquan Zhou 1,  Xin Zhao 2,  Jiemin Lin 2,  Bin Lin 1,  Taotao Lin 1,  Zhi Chen 1,  Zhaohong Chen 3 4,  Zhenyu Wang 5,  Wenge Liu 6
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China.
  • 2 School of Health, Fujian Medical University, Fuzhou, 350108, Fujian, China.
  • 3 Wound Repair Department, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China.
  • 4 Fujian Provincial Key Laboratory of Burn and Trauma, Fuzhou, 350001, Fujian, China.
  • 5 Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China. wzydz@hotmail.com.
  • 6 Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China. 13705977551@163.com.
  • # Contributed equally.
PMID: 33824301 DOI: 10.1038/s41420-021-00455-7
Abstract

Neuron death in spinal cords is caused primarily by Apoptosis after spinal cord injury (SCI). Autophagy can act as a cellular response to maintain neuron homeostasis that can reduce Apoptosis. Although more studies have shown that an epigenetic Enzyme called Lysine-specific demethylase 1 (LSD1) can negatively regulate Autophagy during Cancer research, existing research does not focus on impacts related to LSD1 in nerve injury diseases. This study was designed to determine whether inhibiting LSD1 could enhance Autophagy against Apoptosis and provide effective neuroprotection in vitro and vivo after SCI. The results showed that LSD1 inhibition treatment significantly reduced spinal cord damage in SCI rat models and was characterized by upregulated Autophagy and downregulated Apoptosis. Further research demonstrated that using both pharmacological inhibition and gene knockdown could enhance Autophagy and reduce Apoptosis for in vitro simulation of SCI-caused damage models. Additionally, 3-methyladenine (3-MA) could partially eliminate the effect of Autophagy enhancement and Apoptosis suppression. These findings demonstrated that LSD1 inhibition could protect against SCI by activating Autophagy and hindering Apoptosis, suggesting a potential candidate for SCI therapy.

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