NRF2-regulation in brain health and disease: Implication of cerebral inflammation

被引：328

作者：

Sandberg, Mats ^{[1
]}

Patil, Jaspal ^{[1
]}

D'Angelo, Barbara ^{[2
]}

Weber, Stephen G. ^{[3
]}

Mallard, Carina ^{[2
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Dept Med Biochem & Cell Biol, Inst Biomed, S-40530 Gothenburg, Sweden

[2] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, S-40530 Gothenburg, Sweden

[3] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

来源：

NEUROPHARMACOLOGY | 2014年 / 79卷

基金：

瑞典研究理事会; 美国国家卫生研究院;

关键词：

Neuroinflammation; NRF2; Anti-oxidants; ANTIOXIDANT-RESPONSE-ELEMENT; TRANSCRIPTION FACTOR NRF2; PROTEIN-KINASE-C; OXIDATIVE STRESS; GENE-EXPRESSION; HEME OXYGENASE-1; MEDITERRANEAN DIET; FUNCTIONAL-CHARACTERIZATION; COGNITIVE IMPAIRMENT; SELECTIVE AUTOPHAGY;

D O I：

10.1016/j.neuropharm.2013.11.004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulator of endogenous inducible defense systems in the body. Under physiological conditions NRF2 is mainly located in the cytoplasm. However, in response to oxidative stress, NRF2 translocates to the nucleus and binds to specific DNA sites termed "anti-oxidant response elements" or "electrophile response elements" to initiate transcription of cytoprotective genes. Acute oxidative stress to the brain, such as stroke and traumatic brain injury is increased in animals that are deficient in NRF2. Insufficient NRF2 activation in humans has been linked to chronic diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. New findings have also linked activation of the NRF2 system to anti-inflammatory effects via interactions with NF-kappa B. Here we review literature on cellular mechanisms of NRF2 regulation, how to maintain and restore NRF2 function and the relationship between NRF2 regulation and brain damage. We bring forward the hypothesis that inflammation via prolonged activation of key kinases (p38 and GSK-3 beta) and activation of histone deacetylases gives rise to dysregulation of the NRF2 system in the brain, which contributes to oxidative stress and injury. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：298 / 306

页数：9

共 128 条

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