Journal
ACTA NEUROLOGICA SCANDINAVICA
Volume 102, Issue -, Pages 90-95Publisher
MUNKSGAARD INT PUBL LTD
DOI: 10.1034/j.1600-0404.2000.00313.x
Keywords
Alzheimer's disease; amyloid; therapy; protein conformational disorders
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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 are central to the disease process. However, it is not clear which of the species going from the normal soluble amyloid-beta peptide to the mature amyloid plaque is the toxic agent in the brain. Therefore, an attractive therapeutic strategy for Alzheimer's disease is to block the early steps involving the pathological conversion of the soluble peptide into the abnormally folded oligomeric intermediate precursor of the amyloid fibrils. We have engineered synthetic beta -sheet breaker peptides to bind amyloid-beta peptide, stabilize the normal conformation and destabilize the beta -sheet rich structure of the potentially toxic intermediates and hence the formation of amyloid plaques. Results in vitro, in cell culture and in vivo suggest that beta -sheet breaker peptide may be useful for blocking the pathway that lead to the formation of cerebral amyloid deposits. It remains to be proved that inhibition of the defective folding of amyloid-beta peptide and/or amyloid plaque deposition could be beneficial for the therapeutic treatment of Alzheimer's disease.
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