中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (10): 2190-2191.doi: 10.4103/1673-5374.369107

• 观点:脊髓损伤修复保护与再生 • 上一篇    下一篇

叶酸-接头-药物偶联在脊髓损伤中靶向递送丙烯醛清除剂肼苯哒嗪

  

  • 出版日期:2023-10-15 发布日期:2023-03-28

A perspective on recent findings and future strategies for reactive aldehyde removal in spinal cord injury

Seth A. Herr, Anna J. Prall, Riyi Shi*   

  1. Center for Paralysis Research, Purdue University, West Lafayette, IN, USA (Herr SA, Prall AJ, Shi R) 
    Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA (Herr SA, Prall AJ, Shi R) 
    Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA (Shi R) 
  • Online:2023-10-15 Published:2023-03-28
  • Contact: Riyi Shi, MD, PhD, riyi@purdue.edu.

摘要: https://orcid.org/0000-0002-7297-9428 (Riyi Shi)

Abstract: Acrolein in spinal cord injury: The propensity of reactive aldehydes such as acrolein to both initiate and perpetuate tissue damage after spinal cord injury (SCI) is well established. Formed primarily from lipid peroxidation, acrolein is known to be one of the most reactive aldehydes. Acrolein will quickly overwhelm endogenous clearance mechanisms and antioxidants, and form adducts with lipids, proteins, and DNA. Acrolein is pro-inflammatory and contributes significantly to cellular stress, eventually leading to cell death of neurons (Figure 1). After a neurotrauma, acrolein forms immediately and remains significantly elevated for at least 2 weeks (Burcham, 2017). When injected at physiologically relevant concentrations, acrolein-induced pathologies mirror those seen in trauma (Burcham, 2017). On the other hand, when acrolein is successfully sequestered, significant benefits including reduction of pain, increased locomotion, and restoration of cord tissue structure are observed. Yet, more complete removal of acrolein proves challenging given the high concentrations of acrolein that are generated after injury. There are currently no Food and Drug Administration (FDA)-approved medications for SCI patients that remove acrolein, and promote recovery, despite the known benefits. One of the main challenges of establishing an effective anti-acrolein based therapy for clinical usage is the need for small molecule aldehyde scavengers to cross the blood-brain barrier and do so at concentrations that will remove acrolein effectively without harmful side effects.