Lange Sigrun
Tissue Architecture and Regeneration Research Group, School of Life Sciences, University of Westminster, London, UK.
Neural Regen Res. 2021 May;16(5):934-938. doi: 10.4103/1673-5374.297058.
Peptidylarginine deiminases are a family of calcium-activated enzymes with multifaceted roles in physiological and pathological processes, including in the central nervous system. Peptidylarginine deiminases cause post-translational deimination/citrullination, leading to changes in structure and function of a wide range of target proteins. Deimination can facilitate protein moonlighting, modify protein-protein interaction, cause protein dysfunction and induce inflammatory responses. Peptidylarginine deiminases also regulate the biogenesis of extracellular vesicles, which play important roles in cellular communication through transfer of extracellular vesicle-cargo, e.g., proteins and genetic material. Both peptidylarginine deiminases and extracellular vesicles are linked to a number of pathologies, including in the central nervous system, and their modulation with pharmacological peptidylarginine deiminase inhibitors have shown great promise in several in vitro and in vivo central nervous system disease models. Furthermore, extracellular vesicles derived from mesenchymal stem cells have been assessed for their therapeutic application in central nervous system injury. As circulating extracellular vesicles can be used as non-invasive liquid biopsies, their specific cargo-signatures (including deiminated proteins and microRNAs) may allow for disease "fingerprinting" and aid early central nervous system disease diagnosis, inform disease progression and response to therapy. This mini-review discusses recent advances in the field of peptidylarginine deiminase and extracellular vesicle research in the central nervous system, focusing on several central nervous system acute injury, degeneration and cancer models.
肽基精氨酸脱亚氨酶是一类钙激活酶，在包括中枢神经系统在内的生理和病理过程中具有多方面作用。肽基精氨酸脱亚氨酶可导致翻译后脱亚氨基/瓜氨酸化，从而引起多种靶蛋白的结构和功能变化。脱亚氨基作用可促进蛋白质的兼职功能、改变蛋白质-蛋白质相互作用、导致蛋白质功能障碍并引发炎症反应。肽基精氨酸脱亚氨酶还可调节细胞外囊泡的生物发生，细胞外囊泡通过转运细胞外囊泡货物（如蛋白质和遗传物质）在细胞间通讯中发挥重要作用。肽基精氨酸脱亚氨酶和细胞外囊泡均与包括中枢神经系统疾病在内的多种病理状况相关，并且在多种体外和体内中枢神经系统疾病模型中，用肽基精氨酸脱亚氨酶药理学抑制剂对它们进行调节已显示出巨大潜力。此外，已评估了间充质干细胞衍生的细胞外囊泡在中枢神经系统损伤中的治疗应用。由于循环细胞外囊泡可用作非侵入性液体活检，其特定的货物特征（包括脱亚氨基化蛋白和微小RNA）可能有助于疾病“指纹识别”，辅助中枢神经系统疾病的早期诊断，了解疾病进展以及对治疗的反应。本综述讨论了中枢神经系统中肽基精氨酸脱亚氨酶和细胞外囊泡研究领域的最新进展，重点关注几种中枢神经系统急性损伤、变性和癌症模型。
