Wang Li-Ling, Song Ye-Ping, Mi Jian-Hua, Ding Meng-Lei
Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 201100, China.
Department of Clinical Laboratory, Shanghai East Hospital, School of Medicine, Tongji University, 200120, China.
Med Hypotheses. 2021 Jan;146:110466. doi: 10.1016/j.mehy.2020.110466. Epub 2020 Dec 22.
Alzheimer's disease (AD) is the main cause of dementia, and its pathogenesis is still not clear. Peptidyl arginine deiminases 4(PAD4) as one of the important members of PAD family, is the only protein with nuclear transfer function, it can regulate the expression of many proteins through citrullinating histone. PAD4 can also interact with many transcription factors, involved in regulating gene expression. PAD4 expression is closely related to the inflammatory factors secreted, cell autophagy, tumorigenesis and other neurodegenerative diseases. More importantly, PAD4 and its citrullinated protein were found in cortical and hippocampal neurons of AD patients. To study the expression and regulatory pathway of PAD4 in vivo and in vitro experiments on AD may be of helpful to elucidate the pathogenesis of AD. Meanwhile, detection of anti-citrullinated antibody will have potential value as novel biomarkers of AD.
阿尔茨海默病（AD）是痴呆的主要病因，其发病机制仍不清楚。肽基精氨酸脱亚氨酶4（PAD4）作为PAD家族的重要成员之一，是唯一具有核转位功能的蛋白质，它可通过瓜氨酸化组蛋白来调节多种蛋白质的表达。PAD4还能与许多转录因子相互作用，参与基因表达调控。PAD4的表达与分泌的炎症因子、细胞自噬、肿瘤发生及其他神经退行性疾病密切相关。更重要的是，在AD患者的皮质和海马神经元中发现了PAD4及其瓜氨酸化蛋白。通过体内外实验研究PAD4在AD中的表达及调控途径可能有助于阐明AD的发病机制。同时，检测抗瓜氨酸化抗体作为AD的新型生物标志物将具有潜在价值。
