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MAPKs: new targets for neurodegeneration.

机译：MAPKs：神经变性的新靶标。

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摘要

Neurodegenerative diseases remain a huge unmet pharmaceutical need. For some diseases such as Parkinson's disease, there are currently only palliative therapies, and for others such as Alzheimer's disease there are no proven therapies on the market that have any significant impact on disease progression. Recent work has suggested that cell death may play a key role in a number of neurodegenerative diseases, and halting this aberrant cell death may halt disease progression. Kinases identified in cell death pathways may be attractive targets for neurodegenerative diseases. In this review, the authors will focus on three families of related mitogen-activated protein kinases (MAPKs), namely, the extracellular signal-regulated protein kinases (ERKs), the c-Jun N-terminal kinases (JNKs) and the p38 MAPKs. The evidence for activation of each of these pathways in disease states and in models of neurodegenerative disorders will be examined. Effects of inhibitors, where available, will be discussed, and potential problems and side effects of kinase inhibitors as therapeutics will be addressed.
机译：神经退行性疾病仍然是巨大的未满足的药物需求。对于某些疾病，例如帕金森氏病，目前只有姑息疗法，而对于其他疾病，例如阿尔茨海默氏病，市场上尚无已证明对疾病进展有重大影响的疗法。最近的工作表明，细胞死亡可能在许多神经退行性疾病中起关键作用，而停止这种异常的细胞死亡可能会阻止疾病的进展。在细胞死亡途径中鉴定出的激酶可能是神经退行性疾病的诱人靶标。在这篇综述中，作者将集中研究三个相关的促分裂原激活蛋白激酶（MAPK）家族，即细胞外信号调节蛋白激酶（ERK），c-Jun N端激酶（JNKs）和p38 MAPKs 。将检查在疾病状态和神经退行性疾病模型中激活这些途径的证据。将讨论抑制剂的作用（如果有的话），并讨论激酶抑制剂作为治疗剂的潜在问题和副作用。

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