Targeting p38 MAPK pathway for the treatment of Alzheimer's disease

Accumulating evidence indicates that p38 mitogen-activated protein kinase (MAPK) could play more than one role in Alzheimer's disease (AD) pathophysiology and that patients suffering from AD dementia could benefit from p38 MAPK inhibitors. The p38 MAPK signalling has been widely accepted as a cascade contributing to neuroinflammation. However, deepening insight into the underlying biology of Alzheimer's disease reveals that p38 MAPK operates in other events related to AD, such as excitotoxicity, synaptic plasticity and tau phosphorylation. Although quantification of behavioural improvements upon p38 MAPK inhibition and in vivo evaluation of p38 MAPK significance to various aspects of AD pathology is still missing, the p38 MAPK is emerging as a new Alzheimer's disease treatment strategy. Thus, we present here an update on the role of p38 MAPK in neurodegeneration, with a focus on Alzheimer's disease, by summarizing recent literature and several key papers from earlier years. (C) 2009 Elsevier Ltd. All rights reserved.