Protein Misfolding Disorders Laboratory, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
A growing wealth of evidence indicates that the key pathological event in Alzheimer's disease is the conversion of the normal soluble amyloid-beta peptide into beta-sheet-rich oligomeric structures which have a neurotoxic activity and ability to form insoluble amyloid deposits that accumulate in the brain. Beta-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid-beta peptide and block and/or reverse this abnormal conformational change. In this article we review this approach, describe diverse compounds reported to have this activity and summarize the data supporting the view that beta-sheet breakers could be serious candidates to combat this devastating disease.