GROalpha/KC, a chemokine receptor CXCR2 ligand, can be a potent trigger for neuronal ERK1/2 and PI-3 kinase pathways and for tau hyperphosphorylation-a role in Alzheimer's disease?
Inflammation has been implicated in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative diseases. We have examined the potential role of some chemokine/chemokine receptors in this process. It is known that CXCR2 is a strongly expressed chemokine receptor on neurons and is strongly upregulated in AD in a subpopulation of neuritic plaques. Here, we show that one of the CXCR2 ligand GROalpha/KC can be a potent trigger for the ERK1/2 and PI-3 kinase pathways, as well as tau hyperphosphorylation in the mouse primary cortical neurons. GROalpha immunoreactivity can be detected in a subpopulation of neurons in normal and AD. Therefore, the CXCR2-ligand pair may have a potent pathophysiological role in neurodegenerative diseases.
Xia
MengQi
M
Alzheimer's Research Unit, CAGN 2009, Department of Neurology, Massachusetts General Hospital-East, Harvard Medical School, 144 16th Street, Charlestown, MA, USA.
Hyman
Bradley T
BT
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006133:Growth Substances / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D023063:Receptors, Interleukin-8B; D010566:Virulence Factors, Bordetella; D016875:tau Proteins; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases