Iannaccone Martina, Titta Federica, Serretiello Enrica, De Vivo Giulia, Martin Antonio, Gentile Vittorio
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy.
Recent Pat CNS Drug Discov. 2013 Dec;8(3):235-42. doi: 10.2174/1574889808666131128105630.
Transglutaminases are ubiquitous enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono- or bi-substituted /crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological or pathological processes. For example, neurodegenerative diseases, such as Alzheimer's Disease, Parkinson's Disease, supranuclear palsy, Huntington's Disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. This review focuses on the possible molecular mechanisms responsible for such diseases and on the possible therapeutic effects of selective transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity. The article presents some promising patents on the transglutaminase activity.
转谷氨酰胺酶是一类广泛存在的酶，可催化蛋白质的翻译后修饰。这些酶的主要活性是将蛋白质/肽底物的谷氨酰胺残基与蛋白质/肽共底物的赖氨酸残基交联。除赖氨酸残基外，其他第二亲核共底物可能包括单胺或多胺（形成单取代或双取代/交联加合物）或-OH基团（形成酯键）。在没有共底物的情况下，亲核试剂可能是水，导致谷氨酰胺残基的净脱酰胺作用。转谷氨酰胺酶活性被认为参与了生理或病理过程的分子机制。例如，神经退行性疾病，如阿尔茨海默病、帕金森病、核上性麻痹、亨廷顿病和其他多聚谷氨酰胺疾病，部分特征是大脑中转谷氨酰胺酶活性异常以及受影响大脑中交联蛋白增加。本综述重点关注此类疾病可能的分子机制以及选择性转谷氨酰胺酶抑制剂对转谷氨酰胺酶活性异常疾病患者可能的治疗效果。本文介绍了一些关于转谷氨酰胺酶活性的有前景的专利。
