A beta 42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-beta 42 species and protects synaptic structure and function

作者：Barucker Christian; Bittner Heiko J; Chang Philip K Y; Cameron Scott; Hancock Mark A; Liebsch Filip; Hossain Shireen; Harmeier Anja; Shaw Hunter; Charron Franois M; Gensler Manuel; Dembny Paul; Zhuang Wei; Schmitz Dietmar; Rabe Juergen P; Rao Yong; Lurz Rudi; Hildebrand Peter W; McKinney R Anne; Multhaup Gerhard^*

来源：Scientific Reports, 2015, 5(1): 15410.

DOI：10.1038/srep15410

The amyloid-beta 42 (A beta 42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble A beta 42 oligomers are highly toxic and contribute to progressive neuronal dysfunction, loss of synaptic spine density, and affect long-term potentiation (LTP). We have characterized a short, L-amino acid A beta-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n A beta 42 oligomers, rather than simply inhibiting the aggregation of A beta monomers into oligomers. Our data show that AIP diminishes the loss of A beta 42-induced synaptic spine density and rescues LTP in organotypic hippocampal slice cultures. Notably, the AIP enantiomer (comprised of D-amino acids) attenuated the rough-eye phenotype in a transgenic A beta 42 fly model and significantly improved the function of photoreceptors of these flies in electroretinography tests. Overall, our results indicate that specifically "trapping" low-n oligomers provides a novel strategy for toxic A beta 42-oligomer recognition and removal.

• 出版日期2015-10-29
• 单位河北医科大学