Olsen Ingar, Singhrao Sim K, Potempa Jan
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.
Dementia and Neurodegeneration Research Group, Faculty of Clinical and Biomedical Sciences, University of Central Lancashire, Preston, UK.
J Oral Microbiol. 2018 Jun 22;10(1):1487742. doi: 10.1080/20002297.2018.1487742. eCollection 2018.
Periodontitis, rheumatoid arthritis (RA), atherosclerosis (AS), and Alzheimer's disease (AD) are examples of complex human diseases with chronic inflammatory components in their etiologies. The initial trigger of inflammation that progresses to these diseases remains unresolved. is unique in its ability to secrete the derived peptidyl arginine deiminase (PPAD) and consequently offers a plausible and exclusive link to these diseases through enzymatic conversion of arginine to citrulline. Citrullination is a post-translational enzymatic modification of arginine residues in proteins formed as part of normal physiological processes. However, PPAD has the potential to modify self (bacterial) and host proteins by deimination of arginine amino acid residues, preferentially at the C-terminus. Migration of and/or its secreted PPAD into the bloodstream opens up the possibility that this enzyme will citrullinate proteins at disparate body sites. Citrullination is associated with the pathogenesis of multifactorial diseases such as RA and AD, which have an elusive external perpetrator as they show epidemiological associations with periodontitis. Therefore, PPAD deserves some prominence as an external antigen, in at least, a subset of RA and AD cases, with as yet unidentified, immune/genetic vulnerabilities.
牙周炎、类风湿性关节炎（RA）、动脉粥样硬化（AS）和阿尔茨海默病（AD）是病因中含有慢性炎症成分的复杂人类疾病的例子。进展为这些疾病的炎症的初始触发因素仍未明确。[某种物质]在分泌衍生肽基精氨酸脱亚氨酶（PPAD）方面具有独特能力，因此通过将精氨酸酶促转化为瓜氨酸，为这些疾病提供了一个合理且独特的联系。瓜氨酸化是蛋白质中精氨酸残基的一种翻译后酶促修饰，是正常生理过程的一部分。然而，PPAD有可能通过精氨酸氨基酸残基的脱亚氨基作用，优先在C末端修饰自身（细菌）和宿主蛋白。[某种物质]和/或其分泌的PPAD迁移到血液中，增加了这种酶在不同身体部位使蛋白质瓜氨酸化的可能性。瓜氨酸化与多因素疾病如RA和AD的发病机制相关，这些疾病有一个难以捉摸的外部致病因素，因为它们与牙周炎存在流行病学关联。因此，至少在一部分RA和AD病例中，PPAD作为一种外部抗原值得关注，这些病例存在尚未确定的免疫/遗传易感性。
