GROα/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?

Xia, MengQi; Hyman, Bradley T

« Previous Next »Journal of Neuroimmunology
Volume 122, Issue 1 , Pages 55-64, January 2002

GROα/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?

Alzheimer's Research Unit, CAGN 2009, Department of Neurology, Massachusetts General Hospital-East, Harvard Medical School, 144 16th Street Charlestown, MA 0212, USA

Received 16 July 2000; received in revised form 24 October 2001; accepted 24 October 2001.

Abstract

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 GROα/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. GROα 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.

Keywords: Chemokine receptor, CXCR2, GROα/KC, ERK1/2, PI-3 kinase, Phosphorylated tau