Abstract |
Alzheimer's disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States. Plaques composed of aggregated amyloid-beta protein (Aβ) accumulate between the neural cells in the brain and are associated with dementia and cellular death. Many strategies have been investigated to prevent Aβ self-assembly into disease-associated β-sheet amyloid aggregates; however, a promising therapeutic has not yet been identified. In this study, a peptoid-based mimic of the peptide KLVFF (residues 16-20 of Aβ) was tested for its ability to modulate Aβ aggregation. Peptoid JPT1 includes chiral, aromatic side chains to induce formation of a stable helical secondary structure that allows for greater interaction between the aromatic side chains and the cross β-sheet of Aβ. JPT1 was found to modulate Aβ40 aggregation, specifically decreasing lag time to β-sheet aggregate formation as well as the total number of fibrillar, β-sheet structured aggregates formed. These results suggest that peptoids may be able to limit the formation of Aβ aggregates that are associated with AD.
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Authors | J Phillip Turner, Tammy Lutz-Rechtin, Kelly A Moore, Lauren Rogers, Omkar Bhave, Melissa A Moss, Shannon L Servoss |
Journal | ACS chemical neuroscience
(ACS Chem Neurosci)
Vol. 5
Issue 7
Pg. 552-8
(Jul 16 2014)
ISSN: 1948-7193 [Electronic] United States |
PMID | 24689364
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Amyloid beta-Peptides
- Benzothiazoles
- Peptide Fragments
- Peptoids
- Thiazoles
- amyloid beta-protein (1-40)
- amyloid beta-protein (16-20)
- thioflavin T
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Topics |
- Amyloid beta-Peptides
(chemistry)
- Benzothiazoles
- Binding, Competitive
- Circular Dichroism
- Fluorescence
- Immunoblotting
- Peptide Fragments
(chemistry)
- Peptoids
(chemistry)
- Protein Structure, Secondary
- Thiazoles
(chemistry)
- Time Factors
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