Induction of protein kinase C substrates, Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP), by amyloid beta-protein in mouse BV-2 microglial cells.

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.