Lattanzi Roberta, Miele Rossella
Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
Department of Biochemical Sciences "A. Rossi Fanelli", CNR Institute of Molecular Biology and Pathology, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
Biomedicines. 2021 Nov 9;9(11):1648. doi: 10.3390/biomedicines9111648.
Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction. PKR2 is mainly overexpressed in neurons, whereas PKR1 and PK2 are mainly overexpressed in astrocytes. Once PK2 is released in inflamed tissue, it is involved in both innate and adaptive responses: it triggers macrophage recruitment, production of pro-inflammatory cytokines, and reduction of anti-inflammatory cytokines. Moreover, it modulates the function of T cells through the activation of PKR1 and directs them towards a pro-inflammatory Th1 phenotype. Since the prokineticin system appears to be upregulated following a series of pathological insults leading to neuroinflammation, we will focus here on the involvement of PK2 and PKRs in those pathologies that have a strong underlying inflammatory component, such as: inflammatory and neuropathic pain, Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, obesity, diabetes, and gastrointestinal inflammation.
促动力蛋白是一类新的趋化因子样肽，参与广泛的生物学和病理学活动。特别是，促动力蛋白2（PK2）、促动力蛋白受体1（PKR1）和促动力蛋白受体2（PKR2）在调节神经炎症过程中起核心作用。PK2和PKRs在生理状态下表达水平极低，但在炎症期间会强烈上调，并调节神经元与神经胶质细胞的相互作用。PKR2主要在神经元中过度表达，而PKR1和PK2主要在星形胶质细胞中过度表达。一旦PK2在炎症组织中释放，它就会参与先天性和适应性反应：它触发巨噬细胞募集、促炎细胞因子的产生以及抗炎细胞因子的减少。此外，它通过激活PKR1来调节T细胞的功能，并将它们导向促炎的Th1表型。由于促动力蛋白系统在导致神经炎症的一系列病理损伤后似乎会上调，我们将在此重点关注PK2和PKRs在那些具有强烈潜在炎症成分的疾病中的作用，例如：炎性和神经性疼痛、阿尔茨海默病、帕金森病、多发性硬化症、中风、肥胖症、糖尿病和胃肠道炎症。
