Department of Medical Sciences, Neuroscience and Signalling Laboratory, iBiMED, University of Aveiro, Aveiro, Portugal.
J Alzheimers Dis. 2017;58(4):953-978. doi: 10.3233/JAD-170176.
Altered protein phosphorylation states of several proteins are closely associated with Alzheimer's disease (AD). Among these are the amyloid-β protein precursor (AβPP) and the tau protein. In fact, altered protein phosphorylation states already provide strong biomarkers for AD diagnosis, as is the case with hyperphosphorylated tau. It follows that modulating signaling cascades provides an attractive avenue for exploring novel therapeutic strategies. This review focuses on some of the major protein kinases and protein phosphatases relevant to AD. Of particular relevance, posttranslational modifications dynamically regulate protein activity, subcellular localization, and stability. Protein phosphorylation states can mediate complex formation as well as regulate protein function, and this is important for cellular physiology but can likewise contribute to the development of neuropathological conditions. Furthermore, applying a system approach provides a more comprehensive understanding of the signaling events associated with AD and highlights possible convergence points that may contribute to the different AD pathological hallmarks.
几种蛋白质的磷酸化状态改变与阿尔茨海默病（AD）密切相关。其中包括淀粉样蛋白-β前体（AβPP）和 tau 蛋白。事实上，改变的蛋白质磷酸化状态已经为 AD 的诊断提供了强有力的生物标志物，如过度磷酸化的 tau。因此，调节信号转导途径为探索新的治疗策略提供了一个有吸引力的途径。这篇综述集中讨论了一些与 AD 相关的主要蛋白激酶和蛋白磷酸酶。特别相关的是，翻译后修饰可以动态调节蛋白质的活性、亚细胞定位和稳定性。蛋白质磷酸化状态可以介导复合物的形成，并调节蛋白质的功能，这对于细胞生理学很重要，但同样也可能导致神经病理状况的发展。此外，应用系统方法可以更全面地了解与 AD 相关的信号事件，并突出可能导致不同 AD 病理特征的可能收敛点。
