Screening a specific Zn(ii)-binding peptide for improving the cognitive decline of Alzheimer's disease in APP/PS1 transgenic mice by inhibiting Zn²⁺-mediated amyloid protein aggregation and neurotoxicity

Abstract

PZn screen from phage display technique and PZn loaded nanoparticles inhibiting Aβ aggregation and neurotoxicity in vitro and in vivo.

A Novel Cu(II)-Binding Peptide Identified by Phage Display Inhibits Cu2+-Mediated Aβ Aggregation

“…Aβ immunofluorescence assay was generated as previously described [33]. Briefly, after treatment, the N2a-sw cells were fixed with 4% paraformaldehyde for 30 min.…”

“…Recently, metal-binding peptides selected from phage display libraries as biocompatible metal chelators were shown to be potentially useful for the treatment of AD [33]. The most attractive advantage of phage display technology is that novel peptides for specific targets can be identified without previous knowledge of the interaction between the peptide and the target [34,35].…”

“…In our recent study, we successfully screened a specific Zn(II)-binding peptide based on phage display technology, and identified a Zn(II)-binding peptide that could inhibit Zn 2+ -mediated Aβ aggregation and neurotoxicity, therefore improving cognitive dysfunction in APP/PS1 transgenic mice. We provided a general pipeline for the development of metal chelating agents (for anti-metal-mediated Aβ aggregation) by binding the target metal ion with peptides based on a phage library [33].…”

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

“…48 Self-destructive PEGylated nanosweepers composed of cationic CS captured Aβ and promoted their degradation through cell-mediated autophagy. 49 Metal-phenolic networks-coated AuNPs inhibited Aβ fibrillation, 50 sulfur NPs, 51 and polymerized o-phenylenediamine-derived carbon dots 52 decreased Cu 2+ -mediated Aβ aggregation, while iminodiacetic acid-conjugated, 53 d-penicillamine-capped selenium, 54 and PEG-modified-CS-NPs loaded with a Zn(II)-binding peptide 55 decreased Zn 2+ -mediated Aβ aggregation. MoO 3−x nanodots acted on the same target through the mimic of catalase and SOD activities, 56 and upconversion NPs disrupted amyloid plaques after NIR irradiation.…”

Nasal Delivery of D-Penicillamine Hydrogel Upregulates a Disintegrin and Metalloprotease 10 Expression via Melatonin Receptor 1 in Alzheimer’s Disease Models

“…Major pathological hallmarks of AD are senile plaques (SPs), composed of self-polymerized amyloid-β peptide (Aβ), and neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins (Selkoe, 1991;Hardy and Higgins, 1992). In accordance with the metal hypothesis of AD, Aβ deposition, and tau hyperphosphorylation are aggravated by metal ions, thus promoting the development of AD (Liu et al, 2011;Zhang et al, 2019;Ejaz et al, 2020;Singh et al, 2020;Spotorno et al, 2020). The "metal hypothesis" describes the unbalanced theory of the level and location of metal ions in the pathogenesis of AD (Yang et al, 2019;Patel and Aschner, 2021).…”