Per-6-substituted beta-cyclodextrin libraries inhibit formation of beta-amyloid-peptide (A beta)-derived, soluble oligomers
Alzheimer's disease is the most common cause of dementia in older individuals with compelling evidence favoring neuron dysfunction and death triggered by assembled forms of A beta(1-42). While large neurotoxic amyloid fibrils have been known for years, recent studies show that soluble protofibr...
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Published in | Journal of molecular neuroscience Vol. 19; no. 1-2; pp. 51 - 55 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.08.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Alzheimer's disease is the most common cause of dementia in older individuals with compelling evidence favoring neuron dysfunction and death triggered by assembled forms of A beta(1-42). While large neurotoxic amyloid fibrils have been known for years, recent studies show that soluble protofibril and A beta(1-42)-derived diffusible ligands (ADDLs) may also be involved in neurotoxicity. In the present work, dot-blot immunoassays discriminating ADDLs from monomers were used to screen libraries of per-substituted beta-cyclodextrin (beta-CD) derivatives for inhibition of ADDLs formation. Libraries were prepared from per-6-iodo-beta-CD by treatment with various amine nucleophiles. The most active library tested (containing >2000 derivatives) was derived from imidazole, N, N-dimethylethylenediamine and furfurylamine, which at 10 microM total library, inhibited ADDLs formation (10 nM A beta(1-42)) over a period of 4 hours. The latter was confirmed by a western blot assay showing decreased amounts of the initially formed A beta(1-42) tetramer. These preliminary experiments suggest that derivatized forms of beta-CD can interfere with the oligomerization process of A beta(1-42). |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0895-8696 1559-1166 |
DOI: | 10.1007/s12031-002-0010-x |