College of Light Industry, Liaoning University, Shenyang, 110036, China.
Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, 40227, Taiwan.
Biomed Eng Online. 2018 Apr 24;17(1):46. doi: 10.1186/s12938-018-0477-5.
Neuroinflammation is primarily characterized by overexpression of proinflammatory mediators produced by glial activation or immune cell infiltration. Several kinases have been shown to be critical mediators in neuroinflammation. One of the largest groups of kinases is protein kinases, which have been the second most studied group of drug targets after G-protein-coupled receptors. Thus far, most of the approved kinase inhibitor drugs are adenosine triphosphate-competitive inhibitors with various off-target liabilities because of cross-reactivities; however, marine-derived compounds provide opportunities for discovering allosteric kinase inhibitors. This review summarizes the potential of marine-derived protein kinase inhibitors in the field of neuroinflammatory diseases, such as Parkinson disease, Alzheimer disease, multiple sclerosis, and pain. The previous studies from 1990 to 2017 in this review have shown that marine-derived protein kinase inhibitors have great potential to elicit anti-neuroinflammatory or neuroprotective responses in in vitro and in vivo models of neuroinflammatory diseases. This suggests that further exploration and investigation of these marine-derived protein kinase inhibitors on neuroinflammatory diseases are warranted. Therefore, this review may inspire further discovery of new protein kinase inhibitors from a marine origin and additional neuroscience studies focusing on these valuable marine-derived protein kinase inhibitors.
神经炎症主要表现为神经胶质细胞激活或免疫细胞浸润产生的促炎介质过度表达。已经有几种激酶被证明是神经炎症的关键介质。激酶是最大的激酶组之一，是继 G 蛋白偶联受体之后第二大研究药物靶点组。到目前为止，大多数批准的激酶抑制剂药物都是三磷酸腺苷竞争性抑制剂，由于交叉反应性，存在各种非靶点副作用；然而，海洋来源的化合物为发现变构激酶抑制剂提供了机会。这篇综述总结了海洋来源的蛋白激酶抑制剂在神经炎症性疾病（如帕金森病、阿尔茨海默病、多发性硬化症和疼痛）领域的潜力。本综述中 1990 年至 2017 年的先前研究表明，海洋来源的蛋白激酶抑制剂在神经炎症性疾病的体外和体内模型中具有引发抗神经炎症或神经保护反应的巨大潜力。这表明有必要进一步探索和研究这些海洋来源的蛋白激酶抑制剂对神经炎症性疾病的作用。因此，这篇综述可能会激发人们从海洋来源进一步发现新的蛋白激酶抑制剂，并开展更多关注这些有价值的海洋来源的蛋白激酶抑制剂的神经科学研究。
