Репозиторий Университета

© 2019 Elsevier B.V. While research into the role of cathepsins has been progressing at an exponential pace over the years, research into their respective isoform proteins has been less frenetic. In view of the functional and biological potential of such protein isoforms in model systems for cancer during their initial discovery, much later they have offered a new direction in the field of cathepsin basic and applied research. Consequently, the analysis of such isoforms has laid strong foundations in revealing other important regulatory aspects of the cathepsin proteins in general. In this review article, we address these key aspects of cathepsin isoform proteins, with particular emphasis on how they have shaped what is now known in the context of nuclear cathepsin localization and what potential these hold as nuclear-based therapeutic targets in cancer.

© 2018, Pleiades Publishing, Ltd. Phospholipase D (PLD; EC 3.1.4.4) is one of the key enzymes catalyzing hydrolysis of cell membrane phospholipids. This review considers and summaries current knowledge about six human PLD isoforms, their structure and a role in physiological and pathological processes. Comparative analysis of PLD isoforms structure is presented. The review considers the mechanism of hydrolysis and transphosphatidylation performed by PLD, the role of PLD1 and PLD2 in the pathogenesis of some types of cancer, infectious, thrombotic, and neurodegenerative diseases is analyzed. The prospects of development of PLD isoformselective inhibitors are considered in the context of their clinical use and inclusion into various therapeutic schemes; the latter is especially important in the case of already developed PLD inhibitors. Phosphatidylethanol (PEth) formed in the human body during phospholipid transphosphatidylation catalyzed by PLD is considered as an alcohol abuse biomarker.

© 2018 Russian Academy of Medical Sciences. All rights reserved. Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.