Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Valderrebollo 5, 28041-Madrid , Spain.
Expert Opin Ther Targets. 2014 Jan;18(1):69-77. doi: 10.1517/14728222.2013.843670. Epub 2013 Oct 8.
Glycogen synthase kinase-3 (GSK-3) is recognized as a crucial player in many cellular functions and its activity is tightly controlled by complex mechanisms that are each dependent upon specific signaling pathways. Furthermore, GSK-3 dysfunction has been linked to a number of pathologies, including Alzheimer's disease (AD). In particular, the involvement of GSK-3 in several key pathophysiological pathways leading to AD and neurodegenerative diseases has placed this enzyme in a central position in this disorder.
This article offers a review of the relationship between GSK-3 and AD with a special focus on recent evidence showing a key role of GSK-3 activity in modulating cellular pathways controlling amyloid formation, especially through the control of β-site APP-cleaving enzyme 1 gene expression, as well as its role as a key regulator of neurogenesis.
GSK-3 appears to be a cellular nexus, integrating several signaling systems, including several second messengers and a wide selection of cellular stimulants. The next few years will certainly bring us further insights into the cellular functions of this fascinating enzyme and its potential as a therapeutic target in AD and other neurological disorders.
糖原合成酶激酶-3（GSK-3）被认为在许多细胞功能中起着至关重要的作用，其活性受到复杂机制的严格控制，每种机制都依赖于特定的信号通路。此外，GSK-3 功能障碍与许多病理有关，包括阿尔茨海默病（AD）。特别是 GSK-3 参与导致 AD 和神经退行性疾病的几个关键病理生理途径，使这种酶在这种疾病中处于中心地位。
本文综述了 GSK-3 与 AD 之间的关系，特别关注最近的证据表明 GSK-3 活性在调节控制淀粉样蛋白形成的细胞途径方面发挥着关键作用，特别是通过控制β位点 APP 切割酶 1 基因表达，以及其作为神经发生的关键调节剂的作用。
GSK-3 似乎是一个细胞枢纽，整合了几个信号系统，包括几个第二信使和广泛的细胞刺激物。未来几年肯定会让我们对这种迷人的酶的细胞功能及其在 AD 和其他神经退行性疾病中的治疗靶点潜力有进一步的了解。
