The role of mitogen-activated protein kinase pathways in Alzheimer's disease.
Given the critical role of mitogen-activated protein kinase (MAPK) pathways in regulating cellular processes that are affected in Alzheimer's disease (AD), the importance of MAPKs in disease pathogenesis is being increasingly recognized. All MAPK pathways, i.e., the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 pathways, are activated in vulnerable neurons in patients with AD suggesting that MAPK pathways are involved in the pathophysiology and pathogenesis of AD. Here we review recent findings implicating the MAPK pathways in AD and discuss the relationship between these pathways and the prominent pathological processes, i.e., tau phosphorylation and amyloid-beta deposition, as well as the functional association to amyloid beta protein precursor. We suggest that regulation of these pathways may be a central facet to any potential treatment for the disease.
Zhu
Xiongwei
X
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA. xxz12@po.cwru.edu
Lee
Hyoung-gon
HG
Raina
Arun K
AK
Perry
George
G
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009420:Nervous System / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases
D016564:Amyloid beta-Protein Precursor; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases