RNA aptamers selected against amyloid beta-peptide (Abeta) inhibit the aggregation of Abeta.
Aggregation of amyloid beta-peptide (Abeta) is closely related to the pathogenesis of Alzheimer's disease (AD). Much effort has been devoted to the construction of molecules that suppress and neutralize the toxicity of Abeta. Using a systematic evolution of ligands using the exponential enrichment (SELEX) procedure, we have constructed RNA aptamers that bind to Abeta1-40 and inhibit aggregation. To obtain the RNA aptamers, we applied an oligomer model of Abeta as a selection target using Abeta1-40 conjugated with a colloidal gold nanoparticle (Abeta-AuNP). Although the selected RNA sequences did not converge, two RNA aptamers (N2 and E2) bound more tightly to Abeta-AuNP than the other aptamers. The dissociation constants (K(d)) of and , fluorescent-labeled RNAs, to monomeric Abeta1-40 peptide were estimated as K(d) = 21.6 and 10.9 microM, respectively. ELISA revealed that these aptamers can inhibit Abeta aggregation efficiently. Transmission electron micrographs indicated that and aptamers can stop the fibrillization of Abeta1-40. The selected RNA aptamers may have potential as therapeutic agents for AD pathogenesis.
Takahashi
Tsuyoshi
T
Department of Bioengineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B40, Nagatsuta, Yokohama 226-8501, Japan. ttakahas@bio.titech.ac.jp
Tada
Kosuke
K
Mihara
Hisakazu
H
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005454:Fluorescence Polarization / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry; D015723:Gene Library; D006046:Gold / Q000737:chemistry; D053768:Metal Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D052157:Aptamers, Nucleotide; D005456:Fluorescent Dyes; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D006046:Gold