中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2390-2392.doi: 10.4103/1673-5374.313031

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

Caspase-1：修复潜在神经变性血脑屏障的重要参与者与可能的靶标

  

  • 出版日期:2021-12-15 发布日期:2021-05-13

Caspase-1: an important player and possible target for repair of the blood-brain barrier underlying neurodegeneration

Daniel Rand, Itzik Cooper*   

  1. The Joseph Sagol Neuroscience Center, Sheba Medical Center, Ramat-Gan, Israel (Rand D, Cooper I), Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel (Rand D),School of Psychology, Interdisciplinary Center (IDC), Herzliya, Israel (Cooper I)
    The Nehemia Rubin Excellence in Biomedical Research – The TELEM Program, Sheba Medical Center, Tel-Hashomer, Israel (Cooper I)
  • Online:2021-12-15 Published:2021-05-13
  • Contact: Itzik Cooper, PhD,itzik.cooper@sheba.health.gov.il.
  • Supported by:
    This work was supported by the Defense Threat Reduction Agency-Joint Science & Technology Office for Chemical & Biological Defense (No. 11816372), and the Nehemia Rubin Excellence in Biomedical Research-The TELEM Program supported by the Aaron Gutwirth Fund and by Ministry of Science and Technology (No. 3-13576).

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摘要：

Neural Regen Res：caspase-1：针对血脑屏障神经退行性病变的潜在治疗靶点

     现今老龄化社会正承受着越来越重的脑部疾病负担，尤其是神经退行性疾病。目前还没有有效的神经退行性疾病治疗方法，其主要原因之一就是血脑屏障（BBB）。BBB对于大脑健康至关重要，它可以保护大脑免受毒素的侵害和适当的清除毒素。因此，BBB功能障碍是众多脑部疾病的基础，也成为潜在新疗法的主要靶标。BBB损害的主要常见潜在机制是过度的CNS炎症。反之，血脑屏障损伤也与神经发炎的发生有关，从而结束了恶性循环。多种分子机制显示细胞因子释放和细胞破坏与BBB分解相关，这导致了大脑化学和激素失调，免疫细胞浸润增加，废物清除减少以及依赖于受影响的大脑区域的中枢神经细胞变性，最终导致认知能力下降和其他中枢神经系统疾病。

以色列舍巴医疗中心的Itzik Cooper团队分析了BBB在脑病理学中的功能以及在脑血管部位靶向caspase-1（炎性小体的核心成分）的治疗潜力。他们认为在理想情况下新的治疗方法应该侧重开发治疗通路，可以选择性地干预可改善损伤的炎症反应，同时保护或促进修复。Cooper团队建议利用可以抑制caspase-1的分子靶点作为潜在的治疗靶点，这些靶点可能针对受损的血脑屏障，最终完成大脑修复。

文章在《中国神经再生研究（英文版）》杂志2021年12月12期发表。

https://orcid.org/0000-0003-0723-5542(Itzik Cooper)

Abstract: Our ageing population is bearing an increasing burden on society with an unprecedented rise in brain disease, especially neurodegeneration. Treatment for neurodegeneration is practically non-existent, one major reason being the blood-brain barrier (BBB). The BBB is a crucial component in maintaining a healthy brain as it protects the brain from the entrance of toxins and removes them from the brain’s vicinity, providing proper clearance. Therefore, BBB malfunction is the basis for numerous brain diseases making it a major target for potential new treatments. A major common underlying mechanism for BBB damage is excessive central nervous system (CNS) inflammation. In turn, BBB disruption has been linked to the initiation of neuroinflammation, forming a vicious cycle. The release of cytokines and destruction of cells are associated with BBB breakdown through multiple molecular mechanisms leading to the chemical and hormonal dysregulation of the brain, increased immune cell infiltration, decreased removal of waste, and degeneration of CNS cells that depending on the affected brain region—ultimately lead to cognitive decline and other CNS disorders (Van Dyken and Lacoste, 2018; Figure 1).