Klegeris Andis
Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
Neural Regen Res. 2021 Mar;16(3):423-429. doi: 10.4103/1673-5374.293134.
Sterile inflammatory processes are essential for the maintenance of central nervous system homeostasis, but they also contribute to various neurological disorders, including neurotrauma, stroke, and demyelinating or neurodegenerative diseases. Immune mechanisms in the central nervous system and periphery are regulated by a diverse group of endogenous proteins, which can be broadly divided into the pro-inflammatory damage-associated molecular patterns (DAMPs) and anti-inflammatory resolution-associated molecular patterns (RAMPs), even though there is notable overlap between the DAMP- and RAMP-like activities for some of these molecules. Both groups of molecular patterns were initially described in peripheral immune processes and pathologies; however, it is now evident that at least some, if not all, of these immunomodulators also regulate neuroimmune processes and contribute to neuroinflammation in diverse central nervous system disorders. The review of recent literature demonstrates that studies on DAMPs and RAMPs of the central nervous system still lag behind the much broader research effort focused on their peripheral counterparts. Nevertheless, this review also reveals that over the last five years, significant advances have been made in our understanding of the neuroimmune functions of several well-established DAMPs, including high-mobility group box 1 protein and interleukin 33. Novel neuroimmune functions have been demonstrated for other DAMPs that previously were considered almost exclusively as peripheral immune regulators; they include mitochondrial transcription factor A and cytochrome C. RAMPs of the central nervous system are an emerging area of neuroimmunology with very high translational potential since some of these molecules have already been used in preclinical and clinical studies as candidate therapeutic agents for inflammatory conditions, such as multiple sclerosis and rheumatoid arthritis. The therapeutic potential of DAMP antagonists and neutralizing antibodies in central nervous system neuroinflammatory diseases is also supported by several of the identified studies. It can be concluded that further studies of DAMPs and RAMPs of the central nervous system will continue to be an important and productive field of neuroimmunology.
无菌性炎症过程对于维持中枢神经系统的稳态至关重要,但它们也会导致各种神经系统疾病,包括神经创伤、中风以及脱髓鞘或神经退行性疾病。中枢神经系统和外周的免疫机制受多种内源性蛋白质调节,这些蛋白质大致可分为促炎性损伤相关分子模式(DAMPs)和抗炎性消退相关分子模式(RAMPs),尽管其中一些分子的DAMP样和RAMP样活性存在明显重叠。这两类分子模式最初都是在外周免疫过程和病理中被描述的;然而,现在很明显,这些免疫调节剂中至少有一些(如果不是全部的话)也调节神经免疫过程,并在各种中枢神经系统疾病中导致神经炎症。对近期文献的综述表明,关于中枢神经系统DAMPs和RAMPs的研究仍落后于针对外周对应物的更为广泛的研究工作。尽管如此,该综述也揭示,在过去五年中,我们对几种已确定的DAMPs的神经免疫功能的理解取得了重大进展,包括高迁移率族蛋白B1和白细胞介素33。其他一些以前几乎仅被视为外周免疫调节剂的DAMPs也被证明具有新的神经免疫功能;它们包括线粒体转录因子A和细胞色素C。中枢神经系统的RAMPs是神经免疫学中一个新兴领域,具有很高的转化潜力,因为其中一些分子已在临床前和临床研究中作为炎症性疾病(如多发性硬化症和类风湿性关节炎)的候选治疗药物。一些已确定的研究也支持DAMP拮抗剂和中和抗体在中枢神经系统神经炎症性疾病中的治疗潜力。可以得出结论,对中枢神经系统DAMPs和RAMPs的进一步研究仍将是神经免疫学中一个重要且富有成果的领域。
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