De Vivo G, Gentile V
Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy.
CNS Neurol Disord Drug Targets. 2008 Oct;7(4):370-5. doi: 10.2174/187152708786441821.
Transglutaminases are a large family of related and ubiquitous enzymes which catalyze the cross-linking of a glutaminyl residue of a protein/peptide substrate to a lysyl residue of a protein/peptide co-substrate. These enzymes are also capable of catalyzing other reactions important for the cell viability. The distribution and the physiological roles of the human transglutaminases have been widely studied in numerous cell types and tissues and their roles in several diseases have begun to be identified. Recently, "tissue" transglutaminase (TG2) has been shown to be involved in the molecular mechanisms responsible for a very widespread human pathology, Celiac Disease (CD). Transglutaminase activity has also been hypothesized to be directly involved in the pathogenetic mechanisms responsible for several human neurodegenerative diseases, which are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains, such as Alzheimer's disease (AD), Parkinson's disease (PD), supranuclear palsy, Huntington's disease (HD) and other recently identified polyglutamine diseases. In this review we discuss the biochemistry of the transglutaminases, with particular reference to the molecular mechanisms that could be involved in the physiopathological processes responsible for these human neurodegenerative diseases.
转谷氨酰胺酶是一大类相关且普遍存在的酶，它们催化蛋白质/肽底物的谷氨酰胺残基与蛋白质/肽共底物的赖氨酸残基之间的交联。这些酶还能够催化对细胞活力很重要的其他反应。人类转谷氨酰胺酶的分布和生理作用已在众多细胞类型和组织中得到广泛研究，并且它们在几种疾病中的作用也已开始被确定。最近，“组织”转谷氨酰胺酶（TG2）已被证明参与了导致一种非常普遍的人类疾病——乳糜泻（CD）的分子机制。转谷氨酰胺酶活性也被推测直接参与了导致几种人类神经退行性疾病的发病机制，这些疾病的部分特征是大脑转谷氨酰胺酶活性异常以及受影响大脑中交联蛋白增加，如阿尔茨海默病（AD）、帕金森病（PD）、核上性麻痹、亨廷顿舞蹈病（HD）以及其他最近确定的多聚谷氨酰胺疾病。在这篇综述中，我们讨论转谷氨酰胺酶的生物化学，特别提及可能参与这些人类神经退行性疾病病理生理过程的分子机制。
