Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.
Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.
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DOI：
10.3390/ijms21249357
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发表时间：
2020-12-08
影响因子：
5.6
通讯作者：
Walker DG
中科院分区：
文献类型：
--
作者：
Tsubaki H;Tooyama I;Walker DG
开发新的疾病治疗方法依赖于确定扩大疾病过程所涉及的关键分子靶点。其中一个分子是硫氧还蛋白相互作用蛋白(TXNIP)，也被称为硫氧还蛋白结合蛋白-2(TBP-2)，是α-arrestin蛋白家族的成员，是糖脂代谢的中央调节因子，参与糖尿病相关的血管内皮功能障碍和炎症。TXNIP隔离物减少硫氧还蛋白(Trx)，抑制其功能，导致氧化应激增加。许多不同的细胞应激因素调节TXNIP的表达，包括高糖、内质网应激、自由基、低氧、一氧化氮、胰岛素和腺苷分子。TXNIP还通过与核苷酸结合域、富含亮氨酸的家族和含吡咯结构域-3(NLRP3)的炎症体复合体相互作用，直接参与炎症激活。神经退行性疾病，如阿尔茨海默病，具有与氧化应激、炎症和血管功能障碍相关的重大病理变化。此外，由于葡萄糖和细胞代谢功能障碍与这类脑部疾病有关，血栓素NIP在神经退行性变中的作用已被积极研究。本文就TXNIP在中枢神经系统可能的正常和病理功能的研究现状，从体外培养的神经细胞、人脑和实验动物的研究入手，结合其他研究作一综述。由于TXNIP可由神经元、小胶质细胞、星形胶质细胞和内皮细胞表达，因此提出了大脑中复杂的调节和功能模式。我们将检查表明TXNIP作为神经退行性疾病的治疗靶点的数据，那里需要进一步的研究。
The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer’s disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.
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影响因子：
2.4
作者：
Devi, Takhellambam S.;Yumnamcha, Thangal;Singh, Lalit P.
通讯作者：
Singh, Lalit P.
DOI：
10.1111/j.1432-1033.1983.tb07267.x
发表时间：
1983-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BERSTERMANN, A;VOGT, K;FOLLMANN, H
通讯作者：
FOLLMANN, H
影响因子：
5.3
作者：
Beyer, Marianna M. S.;Lonnemann, Niklas;Korte, Martin
通讯作者：
Korte, Martin
影响因子：
3.6
作者：
Cha-Molstad, Hyunjoo;Xu, Guanlan;Shalev, Anath
通讯作者：
Shalev, Anath
影响因子：
12.8
作者：
Cho, Min Ji;Yoon, Sung-Jin;Min, Jeong-Ki
通讯作者：
Min, Jeong-Ki