The new β amyloid-derived peptide Aβ1-6A2V-TAT(D) prevents Aβ oligomer formation and protects transgenic C. elegans from Aβ toxicity

Neurobiology of Disease
Luisa DiomedeMario Salmona

Abstract

One attractive pharmacological strategy for Alzheimer's disease (AD) is to design small peptides to interact with amyloid-β (Aβ) protein reducing its aggregation and toxicity. Starting from clinical observations indicating that patients coding a mutated Aβ variant (AβA2V) in the heterozygous state do not develop AD, we developed AβA2V synthetic peptides, as well as a small peptide homologous to residues 1-6. These hindered the amyloidogenesis of Aβ and its neurotoxicity in vitro, suggesting a basis for the design of a new small peptide in D-isomeric form, linked to the arginine-rich TAT sequence [Aβ1-6A2V-TAT(D)], to allow translocation across biological membranes and the blood-brain barrier. Aβ1-6A2V-TAT(D) was resistant to protease degradation, stable in serum and specifically able to interfere with Aβ aggregation in vitro, reducing the appearance of toxic soluble species and protecting transgenic C. elegans from toxicity related to the muscular expression of human Aβ. These observations offer a proof of concept for future pharmacological studies in mouse models of AD, providing a foundation for the design of AβA2V-based peptidomimetic molecules for therapeutic purposes.

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Citations

Mar 12, 2017·Journal of Alzheimer's Disease : JAD·Margherita RomeoLuisa Diomede
Sep 9, 2017·Expert Opinion on Therapeutic Patents·Hyemin LeeSung-Hoon Kim
Jul 7, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Ding-Siang HuangJung-Yaw Lin
Oct 13, 2017·ACS Chemical Neuroscience·Edward F GriffinGuy A Caldwell

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