生还是死：PP2A 在中枢神经系统功能中的双重作用、在神经退行性变中的作用及其与脑胰岛素信号的相互作用。
To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.
机构信息
Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
Cell Mol Life Sci. 2019 Jun;76(12):2277-2297. doi: 10.1007/s00018-019-03063-y. Epub 2019 Mar 14.
Abstract
Accumulating evidence has reached the consensus that the balance of phosphorylation state of signaling molecules is a pivotal point in the regulation of cell signaling. Therefore, characterizing elements (kinases-phosphatases) in the phosphorylation balance are at great importance. However, the role of phosphatase enzymes is less investigated than kinase enzymes. PP2A is a member of serine/threonine protein phosphatase that its imbalance has been reported in neurodegenerative diseases. Therefore, we reviewed the superfamily of phosphatases and more specifically PP2A, its regulation, and physiological functions participate in CNS. Thereafter, we discussed the latest findings about PP2A dysregulation in Alzheimer and Parkinson diseases and possible interplay between this phosphatase and insulin signaling pathways. Finally, activating/inhibitory modulators for PP2A activity as well as experimental methods for PP2A study have been reviewed.
摘要
越来越多的证据表明，信号分子磷酸化状态的平衡是细胞信号转导调控的关键点。因此，磷酸化平衡中的特征元素（激酶-磷酸酶）非常重要。然而，磷酸酶酶的作用比激酶酶的作用研究得更少。PP2A 是丝氨酸/苏氨酸蛋白磷酸酶家族的一员，已有报道称其在神经退行性疾病中失衡。因此，我们综述了磷酸酶的超家族，更具体地说，综述了 PP2A 的调节及其在中枢神经系统中的生理功能。然后，我们讨论了 PP2A 在阿尔茨海默病和帕金森病中的失调的最新发现，以及这种磷酸酶与胰岛素信号通路之间可能的相互作用。最后，综述了 PP2A 活性的激活/抑制调节剂以及 PP2A 研究的实验方法。
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