Dataset Information

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

ABSTRACT: The amyloid-?42 (A?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?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?-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n A?42 oligomers, rather than simply inhibiting the aggregation of A? monomers into oligomers. Our data show that AIP diminishes the loss of A?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?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?42-oligomer recognition and removal.

SUBMITTER: Barucker C

PROVIDER: S-EPMC4625140 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function.

Barucker Christian C Bittner Heiko J HJ Chang Philip K-Y PK Cameron Scott S Hancock Mark A MA Liebsch Filip F Hossain Shireen S Harmeier Anja A Shaw Hunter H Charron François M FM Gensler Manuel M Dembny Paul P Zhuang Wei W Schmitz Dietmar D Rabe Jürgen P JP Rao Yong Y Lurz Rudi R Hildebrand Peter W PW McKinney R Anne RA Multhaup Gerhard G

Scientific reports 20151029

The amyloid-β42 (Aβ42) peptide is believed to be the main culprit in the pathogenesis of Alzheimer disease (AD), impairing synaptic function and initiating neuronal degeneration. Soluble Aβ42 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 Aβ-oligomer Interacting Peptide (AIP) that targets a relatively well-defined population of low-n Aβ42 oligomers, ...[more]

PMID: 26510576

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Project description:Micromotor (MM) technology offers a valuable and smart on-the-move biosensing microscale approach in clinical settings where sample availability is scarce in the case of Alzheimer's disease (AD). Soluble amyloid-β protein oligomers (AβO) (mainly AβO42) that circulate in biological fluids have been recognized as a molecular biomarker and therapeutic target of AD due to their high toxicity, and they are correlated much more strongly with AD compared to the insoluble Aβ monomers. A graphene oxide (GO)-gold nanoparticles (AuNPs)/nickel (Ni)/platinum nanoparticles (PtNPs) micromotors (MMGO-AuNPs)-based electrochemical label-free aptassay is proposed for sensitive, accurate, and rapid determination of AβO42 in complex clinical samples such as brain tissue, cerebrospinal fluid (CSF), and plasma from AD patients. An approach that implies the in situ formation of AuNPs on the GO external layer of tubular MM in only one step during MM electrosynthesis was performed (MMGO-AuNPs). The AβO42 specific thiolated-aptamer (AptAβO42) was immobilized in the MMGO-AuNPs via Au-S interaction, allowing for the selective recognition of the AβO42 (MMGO-AuNPs-AptAβO42-AβO42). AuNPs were smartly used not only to covalently bind a specific thiolated-aptamer for the design of a label-free electrochemical aptassay but also to improve the final MM propulsion performance due to their catalytic activity (approximately 2.0× speed). This on-the-move bioplatform provided a fast (5 min), selective, precise (RSD < 8%), and accurate quantification of AβO42 (recoveries 94-102%) with excellent sensitivity (LOD = 0.10 pg mL-1) and wide linear range (0.5-500 pg mL-1) in ultralow volumes of the clinical sample of AD patients (5 μL), without any dilution. Remarkably, our MM-based bioplatform demonstrated the competitiveness for the determination of AβO42 in the target samples against the dot blot analysis, which requires more than 14 h to provide qualitative results only. It is also important to highlight its applicability to the potential analysis of liquid biopsies as plasma and CSF samples, improving the reliability of the diagnosis given the heterogeneity and temporal complexity of neurodegenerative diseases. The excellent results obtained demonstrate the analytical potency of our approach as a future tool for clinical/POCT (Point-of-care testing) routine scenarios.

Dataset Information

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

Publications

Aβ42-oligomer Interacting Peptide (AIP) neutralizes toxic amyloid-β42 species and protects synaptic structure and function.

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