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首页> 外文期刊>Current drug targets. CNS and neurological disorders >Transglutaminases - possible drug targets in human diseases.
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Transglutaminases - possible drug targets in human diseases.

机译：转谷氨酰胺酶-人类疾病中可能的药物靶标。

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Transglutaminases (TGases) belong to a family of closely related proteins that catalyze the cross linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate with the formation of an Nepsilon-(gamma-L-glutamyl)-L-lysine [GGEL] cross link and the concomitant release of ammonia. Such cross-linked proteins are often highly insoluble. Neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), supranuclear palsy and Huntington disease (HD), are characterized in part by aberrant cerebral TGase activity and by increased cross-linked proteins in affected brain. In support of the hypothesis that TGases contribute to neurodegenerative disease, a recent study shows that knocking out TGase 2 in HD-transgenic mice results in increased lifespan. Moreover, recent studies show that cystamine, an in vitro TGase inhibitor, prolongs the lives of HD-transgenic mice. However, these findings are not definitive proof of TGase involvement in HD neuropathology. In neurodegenerative diseases, the brain is under oxidative stress and cystamine can theoretically be converted to the potent antioxidant cysteamine in vivo. Cystamine is also a caspase 3 inhibitor. In addition to neurodegenerative diseases, aberrant TGase activity is associated with celiac disease. Interestingly, a subset of celiac patients develops neurological disorders. This review focuses on the strategies that have been recently employed in the design of TGase inhibitors, and on the possible therapeutic benefits of selective TGase inhibitors to patients with neurodegenerative disorders or to patients with celiac disease.
机译：转谷氨酰胺酶（TGase）属于紧密相关的蛋白质家族，其催化蛋白质/肽底物的谷氨酰胺基残基与蛋白质/肽共底物的赖氨酰残基的交联并形成Nepsilon-（γ-L -谷氨酰-L-赖氨酸[GGEL]交联并伴随释放氨。此类交联蛋白通常高度不溶。神经退行性疾病，例如阿尔茨海默氏病（AD），帕金森病（PD），核上性麻痹和亨廷顿病（HD），部分特征在于异常的大脑TGase活性和受影响的大脑中交联蛋白的增加。为了支持TGase有助于神经退行性疾病的假说，最近的一项研究表明，敲除HD转基因小鼠中的TGase 2可以延长寿命。此外，最近的研究表明，胱胺是一种体外TGase抑制剂，可延长HD转基因小鼠的寿命。但是，这些发现并不是TGase参与高清神经病理学的确切证据。在神经退行性疾病中，大脑处于氧化应激状态，理论上，胱胺可以在体内转化为有效的抗氧化剂半胱胺。胱胺也是caspase 3抑制剂。除神经退行性疾病外，异常的TGase活性与腹腔疾病有关。有趣的是，一部分乳糜泻患者发展为神经系统疾病。这篇综述的重点是最近在设计TGase抑制剂中采用的策略，以及选择性TGase抑制剂对神经退行性疾病或乳糜泻患者可能的治疗益处。

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