Wadhwa Pankaj, Jain Priti, Jadhav Hemant R
Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani- 333031, Rajasthan, India.
Curr Top Med Chem. 2020;20(17):1522-1534. doi: 10.2174/1568026620666200516153136.
Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and GSK3β. However, GSK3β is highly expressed in different areas of the brain and has been implicated in Alzheimer's disease as it is involved in tau phosphorylation. Due to its high specificity concerning substrate recognition, GSK3 has been considered as an important target. In the last decade, several GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the information published in the last decade about the role of GSK3 in Alzheimer's disease and progress in the development of its inhibitors. Using this collated information, medicinal chemists can strategize and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer's disease.
糖原合酶激酶3（GSK3）是丝氨酸/苏氨酸蛋白激酶之一，因其在多种信号通路中的作用而备受关注。它有两种亚型，即GSK3α和GSK3β。然而，GSK3β在大脑的不同区域高度表达，并且由于其参与tau蛋白磷酸化而与阿尔茨海默病有关。由于其在底物识别方面具有高度特异性，GSK3被认为是一个重要的靶点。在过去十年中，已经报道了几种GSK3抑制剂，并且有两种分子正在进行临床试验。这篇综述整理了过去十年中发表的关于GSK3在阿尔茨海默病中的作用及其抑制剂开发进展的信息。利用这些整理好的信息，药物化学家可以制定策略并设计出可能对治疗阿尔茨海默病有用的新型GSK3抑制剂。
