Implication of the Kallikrein-Kinin system in neurological disorders: Quest for potential biomarkers and mechanisms.
Implication of the Kallikrein-Kinin system in neurological disorders: Quest for potential biomarkers and mechanisms.
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DOI：
10.1016/j.pneurobio.2018.01.003
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发表时间：
2018-06
影响因子：
6.7
通讯作者：
Kobeissy F
中科院分区：
文献类型：
--
作者：
Nokkari A;Abou-El-Hassan H;Mechref Y;Mondello S;Kindy MS;Jaffa AA;Kobeissy F
神经系统疾病在全球范围内的合并症和死亡率方面代表了主要的健康问题。尽管我们对疾病进展和预防所涉及的病理生理过程的理解有了巨大的增加，但迄今为止积累的知识在治疗干预和增强临床结局方面产生了相对温和的转化益处。针对特定的神经分子通路，不同的策略已被调整为针对这些疾病的发展和进展。激肽释放酶-激肽系统（KKS）是最具描述性的候选系统之一，因为其普遍存在的作用介导这些神经系统疾病的几种病理生理学特征以及涉及调节各种脑功能。几种实验性KKS模型显示，抑制或刺激KKS系统的两种受体（B1 R和B2 R）可以表现出神经保护和/或不良病理结果。这篇更新的综述提供了KKS组分及其在不同神经系统疾病中的功能的背景细节，包括颞叶癫痫、创伤性脑损伤、中风、脊髓损伤、阿尔茨海默病、多发性硬化和神经胶质瘤。最后，这项工作将突出KKS组分作为潜在神经治疗靶点的假定作用，并提供未来将这些发现转化为神经系统疾病潜在临床生物标志物的可能性的观点。
Neurological disorders represent major health concerns in terms of comorbidity and mortality worldwide. Despite a tremendous increase in our understanding of the pathophysiological processes involved in disease progression and prevention, the accumulated knowledge so far resulted in relatively moderate translational benefits in terms of therapeutic interventions and enhanced clinical outcomes. Aiming at specific neural molecular pathways, different strategies have been geared to target the development and progression of such disorders. The kallikrein-kinin system (KKS) is among the most delineated candidate systems due to its ubiquitous roles mediating several of the pathophysiological features of these neurological disorders as well as being implicated in regulating various brain functions. Several experimental KKS models revealed that the inhibition or stimulation of the two receptors of the KKS system (B1R and B2R) can exhibit neuroprotective and/or adverse pathological outcomes. This updated review provides background details of the KKS components and their functions in different neurological disorders including temporal lobe epilepsy, traumatic brain injury, stroke, spinal cord injury, Alzheimer’s disease, multiple sclerosis and glioma. Finally, this work will highlight the putative roles of the KKS components as potential neurotherapeutic targets and provide future perspectives on the possibility of translating these findings into potential clinical biomarkers in neurological disease.
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