Inhibition of c-Jun N-terminal kinase increases apoE expression in vitro and in vivo.
Apolipoprotein E (apoE), a ligand for the low-density lipoprotein receptor family, has been implicated in modulating glial inflammatory responses and the risk of neurodegeneration associated with Alzheimer's disease. Glial cells activated by lipopolysaccharide (LPS) have decreased apoE levels and we recently showed that apoE itself can modulate the inflammatory response by reducing c-Jun N-terminal kinase (JNK) activation. Reduced JNK phosphorylation is vital to overcome the LPS-induced decrease in apoE expression, suggesting that JNK inhibition may be an effective way to increase apoE protein and protract its anti-inflammatory properties. This study investigates the impact of JNK inhibition on apoE production using two JNK inhibitors. Our work in primary glia and in vivo in mice injected with JNK inhibitor demonstrates that inhibition of JNK may be an effective way to increase apoE expression.
Pocivavsek
Ana
A
Department of Neuroscience, Georgetown University, 3970 Reservoir Road NW, Washington, DC 20057-1464, USA.
Rebeck
G William
GW
D000544:Alzheimer Disease / Q000201:enzymology*; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis*; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
D001057:Apolipoproteins E; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases