The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease.
The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease.
复制标题
DOI：
10.1155/2012/649079
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Eales KL
中科院分区：
文献类型：
--
作者：
Corrêa SA;Eales KL
大量证据表明 p38 丝裂原激活蛋白激酶 (MAPK) 信号级联在突触可塑性和神经退行性疾病中发挥着至关重要的作用。在这篇综述中，我们将讨论 p38 MAPK 的细胞定位和激活，以及其底物 MAPKAPK 2 (MK2) 和 tau 蛋白的分子和细胞机制的最新进展。我们将特别关注 p38 MAPK-MK2 和 p38 MAPK-tau 激活轴在控制神经炎症、肌动蛋白重塑和 tau 过度磷酸化方面的理解，这些过程被认为与正常衰老以及神经退行性疾病有关。我们还将深入探讨阐明 p38 MAPK-MK2 和 p38 MAPK-tau 信号级联的精确作用如何有助于确定新的治疗靶点，以减缓阿尔茨海默病和帕金森病等神经退行性疾病中观察到的症状。
A significant amount of evidence suggests that the p38-mitogen-activated protein kinase (MAPK) signalling cascade plays a crucial role in synaptic plasticity and in neurodegenerative diseases. In this review we will discuss the cellular localisation and activation of p38 MAPK and the recent advances on the molecular and cellular mechanisms of its substrates: MAPKAPK 2 (MK2) and tau protein. In particular we will focus our attention on the understanding of the p38 MAPK-MK2 and p38 MAPK-tau activation axis in controlling neuroinflammation, actin remodelling and tau hyperphosphorylation, processes that are thought to be involved in normal ageing as well as in neurodegenerative diseases. We will also give some insight into how elucidating the precise role of p38 MAPK-MK2 and p38 MAPK-tau signalling cascades may help to identify novel therapeutic targets to slow down the symptoms observed in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.