title: A peptide that binds specifically to the β-amyloid of Alzheimer's disease: selection and assessment of anti-β-amyloid neurotoxic effects.
abstract: The accumulation of the amyloid-β peptide (Aβ) into amyloid plaques, an essential event in Alzheimer's disease (AD) pathogenesis, has caused researchers to seek compounds that physiologically bind Aβ and modulate its aggregation and neurotoxicity. In order to develop new Aβ-specific peptides for AD, a randomized 12-mer peptide library with Aβ₁₋₁₀ as the target was used to identify peptides in the present study. After three rounds of selection, specific phages were screened, and their binding affinities to Aβ₁₋₁₀ were found to be highly specific. Finally, a special peptide was synthesized according to the sequences of the selected phages. In addition, the effects of the special peptide on Aβ aggregation and Aβ-mediated neurotoxicity in vitro and in vivo were assessed. The results show that the special peptide not only inhibited the aggregation of Aβ into plaques, but it also alleviated Aβ-induced PC12 cell viability and apoptosis at appropriate concentrations as assessed by the cell counting kit-8 assay and propidium iodide staining. Moreover, the special peptide exhibited a protective effect against Aβ-induced learning and memory deficits in rats, as determined by the Morris water maze task. In conclusion, we selected a peptide that specifically binds Aβ₁₋₁₀ and can modulate Aβ aggregation and Aβ-induced neuronal damage. This opens up possibilities for the development of a novel therapeutic approach for the treatment of AD.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Xian-Ling
authors.initials: XL
authors.lastname: Zhou
authors.forename: Qi-Gang
authors.initials: QG
authors.lastname: Yang
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
authors.forename: Gui-Hai
authors.initials: GH
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D008297:Male; D018782:Maze Learning; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D010446:Peptide Fragments / Q000378:metabolism*; D019151:Peptide Library; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D019151:Peptide Library
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