Protein kinases CK1 and CK2 as new targets for neurodegenerative diseases

基诺美 酪蛋白激酶1 激酶 肌萎缩侧索硬化 药物发现 生物 小分子 神经科学 神经退行性变 医学 药品 药理学 计算生物学 生物信息学 蛋白激酶A 疾病 生物化学 病理
作者
Daniel I. Pérez,Carmen Gil,Ana Martı́nez
出处
期刊:Medicinal Research Reviews [Wiley]
卷期号:31 (6): 924-954 被引量:143
标识
DOI:10.1002/med.20207
摘要

Following the discovery of the human kinome, protein kinases have become the second most important group of drug targets as they can be modulated by small ligand molecules. Moreover, orally active protein kinase inhibitors have recently reached the market and there are many more in clinical trials. The lack of treatments for neurodegenerative diseases has increased human and financial efforts in the search for new therapeutic targets that could provide new effective drug candidates. The importance of kinases in the molecular pathway of neuronal survival is under study, but different key pathways have been described. New roles for the old casein kinases 1 and 2, currently known as protein kinases CK1 and CK2, have recently been discovered in the molecular pathology of different neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. The search for specific inhibitors of these enzymes has become an important challenge for the treatment of these devastating diseases. The role of these two kinases in the molecular pathology of different neurodegenerative diseases together with different chemical families that are able to more or less specifically inhibit CK1 and CK2 are discussed in this review.

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