%0 Journal Article
%T The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease
%A S£¿nia A. L. Corr¨ºa
%A Katherine L. Eales
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/649079
%X 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. 1. Introduction The MAPKs are a specific class of serine/threonine kinases which respond to extracellular signals such as growth factors, mitogens, and cellular stress and mediate proliferation, differentiation, and cell survival in mammalian cells. There are 4 distinct groups of MAPKs within mammalian cells: the extracellular signal-related kinases (ERKs), the c-jun N-terminal kinases (JNKs), the atypical MAPKs (ERK3, ERK5, and ERK8), and the p38 MAPKs [1]. The p38 MAPKs are described as stress-activated protein kinases as they are primarily activated through extracellular stresses and cytokines and consequently have been extensively studied in the field of inflammation. There are, however, numerous additional roles of p38 MAPK which are becoming of interest, including the role that the p38 MAPK signalling pathway plays in neuronal function such as synaptic plasticity and neurodegenerative disease. In the present paper we will give an overview of p38 MAPK localisation, activation, and the functional role of this signalling cascade in the mammalian brain, especially the activation of the p38 MAPK cascade during synaptic plasticity in the hippocampus. Although p38 MAPK isoforms have been shown to be highly expressed in the brain, only a handful of brain-specific substrates for p38 MAPK have been characterised in vivo. In this paper we will especially focus our attention on the role of two p38 MAPK substrates in neurons: MAPK-activated protein kinase 2 (MAPKAPK-2, also known as MK2) and tau protein. The involvement of the p38 MAPK-MK2 and p38 MAPK-tau signalling cascades in neuroinflammation, actin
%U http://www.hindawi.com/journals/jst/2012/649079/