Practical assay and molecular mechanism of aggregation inhibitors of beta-amyloid.
Beta-Amyloid peptide (Abeta) is the main protein component of neuritic plaques in the brain of patients of Alzheimer's disease (AD), and its neurotoxicity would be exposed by the formation of aggregates. The aggregation inhibitors composed of an Abeta recognition element (KLVFF) and a hydrophilic moiety are evaluated by a novel fluorescence assay. These compounds inhibit growth of the model aggregates on the KLVFF immobilized surface. In addition, some compounds also possess disrupting activities of preformed aggregates. These compounds could be a key candidate for therapeutic drugs for AD by their novel molecular mechanisms.
Akikusa
S
S
National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, Japan.
Watanabe
K-I
KI
Horikawa
E
E
Nakamura
K
K
Kodaka
M
M
Okuno
H
H
Konakahara
T
T
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000633:toxicity; D001667:Binding, Competitive; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D009842:Oligopeptides