Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy.
Curr Med Chem. 2022;29(27):4631-4697. doi: 10.2174/0929867329666220216113517.
GSK-3β activity has been strictly related to neuroinflammation and neurodegeneration. Alzheimer's disease is the most studied neurodegenerative disease, but GSK-3β seems to be involved in almost all neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, and the autoimmune disease multiple sclerosis.
This review aims to help researchers both working on this research topic or not to have a comprehensive overview of GSK-3β in the context of neuroinflammation and neurodegeneration.
Literature has been searched using PubMed and SciFinder databases by inserting specific keywords. A total of more than 500 articles have been discussed.
First of all, the structure and regulation of the kinase were briefly discussed, and then, specific GSK-3β implications in neuroinflammation and neurodegenerative diseases were illustrated with the help of figures, to conclude with a comprehensive overview on the most important GSK-3β and multitarget inhibitors. The structure and IC values at the target kinase have been reported for all the discussed compounds.
GSK-3β is involved in several signaling pathways in neurons, glial cells and immune cells. The fine regulation and interconnection of all these pathways are at the base of the rationale use of GSK-β inhibitors in neuroinflammation and neurodegeneration. Some compounds are now under clinical trials. Despite this, the compounds' pharmacodynamic and ADME/Tox profiles were often not fully characterized which is deleterious in such a complex system.
GSK-3β 的活性与神经炎症和神经退行性变密切相关。阿尔茨海默病是研究最多的神经退行性疾病，但 GSK-3β 似乎与几乎所有的神经退行性疾病有关，包括帕金森病、肌萎缩侧索硬化症、额颞叶痴呆、亨廷顿病和自身免疫性疾病多发性硬化症。
本文旨在帮助从事这一研究课题的研究人员或不从事这一研究课题的人员全面了解 GSK-3β 在神经炎症和神经退行性变中的作用。
通过在 PubMed 和 SciFinder 数据库中插入特定的关键词，检索文献。共讨论了 500 多篇文章。
首先简要讨论了激酶的结构和调控，然后借助图表说明了 GSK-3β 在神经炎症和神经退行性疾病中的具体作用，最后对最重要的 GSK-3β 和多靶点抑制剂进行了全面概述。报告了所有讨论化合物的结构和靶激酶的 IC 值。
GSK-3β 参与神经元、神经胶质细胞和免疫细胞中的几种信号通路。所有这些途径的精细调控和相互联系是合理使用 GSK-β 抑制剂治疗神经炎症和神经退行性变的基础。一些化合物目前正在进行临床试验。尽管如此，这些化合物的药效学和 ADME/Tox 特征往往没有得到充分的描述，这在如此复杂的系统中是有害的。
