Beta-sheet breakers for Alzheimer's disease therapy.
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.
Protein Misfolding Disorders Laboratory, Department of Neurology, University of Texas Medical Branch, Galveston, TX, USA.
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D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000009:adverse effects / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008954:Models, Biological; D010446:Peptide Fragments / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C442220:amyloid beta-protein (2-42)