The plasma membrane: a target and hurdle for the development of anti-Abeta drugs?

The plasma membrane has been the subject of intense investigation in the search for anti-amyloidogenic drugs for the treatment of Alzheimer's disease. Studies have highlighted numerous toxic properties of the well-known amyloid Abeta peptide on neuronal membranes. In this respect recent experimental data suggest that an early step in amyloid toxicity might be intracellularly mediated. This suggests that effective anti-amyloidogenic agents must be able to readily cross the plasma membrane while at the same time, counteracting the deleterious effects of the Abeta peptide on the phospholipid bilayer. This review summarizes recent findings regarding amyloid-plasma membrane interactions and discusses their relevance for the design of novel, potential anti-Abeta drugs.