Several lines of evidence suggest that the ATP binding cassette A1 (ABCA1) is also involved in other degenerative processes such as brain neurodegeneration. Cholesterol and cAMP activate ABCA1 in a cell-specific manner. We employed a cell culture model of murine monocytes (P388) and neuroblastoma cells (N2A) and studied the differential induction of the ABCA1-gene product by modifying the cholesterol acceptor and by inhibition of the MAP-kinase pathway. Our study reveals a rise of ABCA1-expression in both N2A and P388 by cAMP. This increase is accompanied by a higher activation of the MAP-kinase-pathway. The inhibition of the MAP-kinase activation disrupts the stimulating effect of cAMP but increases the base line expression of ABCA1. Our data suggest a negative feedback between the MAP-kinase-system and ABCA1. We conclude that the interaction of the MAP-kinase pathway and the ABCA1 system might affect the function of neuronal and microglial cells in the brain. (C) 2007 Elsevier Inc. All rights reserved.