A growing wealth of evidence indicates that the key pathological event in Alzheimers disease is the conversion of the normal soluble amyloid-β peptide into β-sheet-rich oligomeric structures which have a neurotoxic activity and ability to form insoluble amyloid deposits that accumulate in the brain. b-sheet breakers constitute a new class of drugs that are designed to specifically bind amyloid-β 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 b-sheet breakers could be serious candidates to combat this devastating disease.
alzheimer disease, amyloid, therapy
Protein Misfolding Disorders Laboratory, Department of Neurology, University of Texas Medical Branch,Galveston, TX, USA