Beta‐sheet breaker strategy for the treatment of Alzheimer's disease

Abstract

Abstract Alzheimer's disease is a degenerative disorder of the brain for which there is no cure or effective treatment. Recent studies suggest that cerebral amyloid plaques play a central role in the pathogenesis of the disease. An attractive therapeutic strategy for Alzheimer's disease is to block the early steps of misfolding and aggregation of the soluble amyloid‐beta peptide. We have engineered synthetic β‐sheet breaker peptides to bind amyloid‐β peptide, stabilize the normal conformation, and destabilize the β‐sheet rich structure that leads to the formation of amyloid plaques. Results in vitro, in cell culture, and in vivo suggest that β‐sheet breaker peptide may be useful for blocking the process of cerebral amyloid deposition. Chemical modifications were introduced into the active peptides to improve their pharmacological properties. It remains to be proved that inhibition of the pathway leading to amyloid plaque deposition could be beneficial for the therapeutic treatment of Alzheimer's disease. Drug Dev. Res. 56:184–193, 2002. © 2002 Wiley‐Liss, Inc.