Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier.

IF 5.9 1区医学 Q1 NEUROSCIENCES

Fluids and Barriers of the CNS Pub Date : 2024-11-21 DOI:10.1186/s12987-024-00599-5

Eduardo Cazalla, Antonio Cuadrado, Ángel Juan García-Yagüe

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引用次数: 0

Abstract

Background: The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional throughout oxidative stress and inflammation, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases.

Main body: Maintaining BBB integrity is of utmost importance in preventing a wide range of neurological disorders. NRF2 is the main transcription factor that regulates cellular redox balance and inflammation-related gene expression. It has also demonstrated a potential role in regulating tight junction integrity and contributing to the inhibition of ECM remodeling, by reducing the expression of several metalloprotease family members involved in maintaining BBB function. Overall, we review current insights on the role of NRF2 in addressing protection against the effects of BBB dysfunction, discuss its involvement in BBB maintenance in different neuropathological diseases, as well as, some of its potential activators that have been used in vitro and in vivo animal models for preventing barrier dysfunction.

Conclusions: Thus, emerging evidence suggests that upregulation of NRF2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase its protection.

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转录因子 NRF2 在维持血脑屏障完整性中的作用。

背景：血脑屏障（BBB血脑屏障（BBB）是调节血液与中枢神经系统之间分子和细胞交换的复杂而动态的界面。它在整个结构和功能上都会受到氧化应激和炎症的影响，这可能会损害其完整性并导致神经退行性疾病的发病机制：保持 BBB 的完整性对于预防各种神经系统疾病至关重要。NRF2 是调节细胞氧化还原平衡和炎症相关基因表达的主要转录因子。它还通过减少参与维持 BBB 功能的几种金属蛋白酶家族成员的表达，在调节紧密连接完整性和抑制 ECM 重塑方面发挥了潜在作用。总之，我们回顾了目前对 NRF2 在保护机体免受 BBB 功能障碍影响方面作用的认识，讨论了它在不同神经病理疾病中参与 BBB 维护的情况，以及它在体外和体内动物模型中用于预防屏障功能障碍的一些潜在激活剂：因此，新出现的证据表明，上调 NRF2 及其靶基因可抑制氧化应激和神经炎症，恢复 BBB 的完整性并增强其保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).