Murphy Anne, Sunohara Janet R, Sundaram Meenakshi, Ridgway Neale D, McMaster Christopher R, Cook Harold W, Byers David M
Department of Pediatrics, Atlantic Research Centre, Dalhousie University, Room C-305 Clinical Research Centre, 5849 University Avenue, Halifax, NS B3H 4H7, Canada.
Neurosci Lett. 2003 Aug 14;347(1):9-12. doi: 10.1016/s0304-3940(03)00648-7.
Microglial activation by amyloid beta-protein in senile plaques contributes to neurodegeneration in Alzheimer disease. In BV-2 microglial cells, amyloid beta-protein 1-40 (Abeta 1-40) elicited a dose-dependent increase (3-4 fold) of Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP), two protein kinase C substrates implicated in membrane-cytoskeletal alterations underlying microglial adhesion, migration, secretion, and phagocytosis. Neither MARCKS nor MRP was induced by the amyloid fragment Abeta 25-35, although both Abeta 1-40 and Abeta 25-35 caused extensive aggregation of BV-2 cells. Interferon-gamma synergistically enhanced the induction by Abeta 1-40 of inducible nitric oxide synthase, but not MARCKS or MRP. Our results suggest that MARCKS and MRP may play important roles in microglia activated by amyloid peptides.
