Fakhri Sajad, Mohammadi Pour Pardis, Piri Sana, Farzaei Mohammad Hosein, Echeverría Javier
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Front Pharmacol. 2021 Oct 26;12:742146. doi: 10.3389/fphar.2021.742146. eCollection 2021.
Growing studies are revealing the critical manifestations of influenza, dengue virus (DENV) infection, Zika virus (ZIKV) disease, and Ebola virus disease (EVD) as emerging infectious diseases. However, their corresponding mechanisms of major complications headed for neuronal dysfunction are not entirely understood. From the mechanistic point of view, inflammatory/oxidative mediators are activated during emerging infectious diseases towards less cell migration, neurogenesis impairment, and neuronal death. Accordingly, the virus life cycle and associated enzymes, as well as host receptors, cytokine storm, and multiple signaling mediators, are the leading players of emerging infectious diseases. Consequently, chemokines, interleukins, interferons, carbohydrate molecules, toll-like receptors (TLRs), and tyrosine kinases are leading orchestrates of peripheral and central complications which are in near interconnections. Some of the resulting neuronal manifestations have attracted much attention, including inflammatory polyneuropathy, encephalopathy, meningitis, myelitis, stroke, Guillain-Barré syndrome (GBS), radiculomyelitis, meningoencephalitis, memory loss, headaches, cranial nerve abnormalities, tremor, and seizure. The complex pathophysiological mechanism behind the aforementioned complications urges the need for finding multi-target agents with higher efficacy and lower side effects. In recent decades, the natural kingdom has been highlighted as promising neuroprotective natural products in modulating several dysregulated signaling pathways/mediators. The present study provides neuronal manifestations of some emerging infectious diseases and underlying pathophysiological mechanisms. Besides, a mechanistic-based strategy is developed to introduce candidate natural products as promising multi-target agents in combating major dysregulated pathways towards neuroprotection in influenza, DENV infection, ZIKV disease, and EVD.
越来越多的研究揭示了流感、登革热病毒（DENV）感染、寨卡病毒（ZIKV）病和埃博拉病毒病（EVD）作为新发传染病的关键表现。然而，它们导致神经功能障碍的主要并发症的相应机制尚未完全明了。从机制角度来看，在新发传染病期间，炎症/氧化介质被激活，导致细胞迁移减少、神经发生受损和神经元死亡。因此，病毒生命周期及相关酶、宿主受体、细胞因子风暴和多种信号介质是新发传染病的主要因素。因此，趋化因子、白细胞介素、干扰素、碳水化合物分子、Toll样受体（TLR）和酪氨酸激酶是外周和中枢并发症的主要协调者，它们之间存在密切联系。一些由此产生的神经表现引起了广泛关注，包括炎性多发性神经病、脑病、脑膜炎、脊髓炎、中风、格林-巴利综合征（GBS）、神经根脊髓炎、脑膜脑炎、记忆丧失、头痛、颅神经异常、震颤和癫痫发作。上述并发症背后复杂的病理生理机制促使人们需要寻找疗效更高、副作用更低的多靶点药物。近几十年来，天然产物被认为是有望调节多种失调信号通路/介质的神经保护天然产物。本研究阐述了一些新发传染病的神经表现及其潜在的病理生理机制。此外，还制定了一种基于机制的策略，以引入候选天然产物作为有前景的多靶点药物，来对抗流感、DENV感染、ZIKV病和EVD中导致神经保护失调的主要信号通路。
