Baier Andrea, Szyszka Ryszard
Institute of Biological Sciences, The John Paul II Catholic University of Lublin, Lublin, Poland.
Front Mol Biosci. 2022 Oct 6;9:916063. doi: 10.3389/fmolb.2022.916063. eCollection 2022.
Casein kinases are involved in a variety of signaling pathways, and also in inflammation, cancer, and neurological diseases. Therefore, they are regarded as potential therapeutic targets for drug design. Recent studies have highlighted the importance of the casein kinase 1 superfamily as well as protein kinase CK2 in the development of several neurodegenerative pathologies, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. CK1 kinases and their closely related tau tubulin kinases as well as CK2 are found to be overexpressed in the mammalian brain. Numerous substrates have been detected which play crucial roles in neuronal and synaptic network functions and activities. The development of new substances for the treatment of these pathologies is in high demand. The impact of these kinases in the progress of neurodegenerative disorders, their bona fide substrates, and numerous natural and synthetic compounds which are able to inhibit CK1, TTBK, and CK2 are discussed in this review.
酪蛋白激酶参与多种信号通路,也与炎症、癌症和神经疾病有关。因此,它们被视为药物设计的潜在治疗靶点。最近的研究强调了酪蛋白激酶1超家族以及蛋白激酶CK2在几种神经退行性疾病(如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症)发展过程中的重要性。人们发现CK1激酶及其密切相关的tau微管蛋白激酶以及CK2在哺乳动物大脑中过度表达。已检测到许多在神经元和突触网络功能及活动中起关键作用的底物。迫切需要开发用于治疗这些疾病的新物质。本综述讨论了这些激酶在神经退行性疾病进展中的作用、它们的真正底物以及许多能够抑制CK1、TTBK和CK2的天然和合成化合物。