Fibril Growth Behavior of Amyloid β on Polymer-Based Planar Membranes: Implications for the Entanglement and Hydration of Polymers

Shimanouchi, Toshinori; Iwamura, Miki; Deguchi, Shintaro; Kimura, Yukitaka

doi:10.3390/app11104408

Cited by 3 publications

(1 citation statement)

References 55 publications

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“…We were then in a position to leverage the peptides that had been designed and tested to address the ultimate aim of the studyto throw light on the mechanism of Aβ42 neurotoxicity, currently believed to be driven by interactions between Aβ42 oligomers and membrane phospholipids. To this end, we used a model system comprising artificial phospholipid membranes mimicking plasma and mitochondrial membranes, − as has been done previously. For example, Press-Sandler and Miller used a model system of 1,2-dioleoyl- sn -glycero3-phosphocholine (DOPC) lipids, which mimic plasma membrane phospholipids, to follow the behavior of Aβ42 dimers upon insertion into DOPC lipid vesicles.…”

Section: Introductionmentioning

confidence: 99%

APPI-Derived Cyclic Peptide Enhances Aβ42 Aggregation and Reduces Aβ42-Mediated Membrane Destabilization and Cytotoxicity

Lacham-Hartman,

Moshe,

Ben-Zichri

et al. 2023

ACS Chem. Neurosci.

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An amyloid precursor protein inhibitor (APPI) and amyloid beta 42 (Aβ42) are both subdomains of the human transmembrane amyloid precursor protein (APP). In the brains of patients with Alzheimer's disease (AD), Aβ42 oligomerizes into aggregates of various sizes, with intermediate, low-molecular-weight Aβ42 oligomers currently being held to be the species responsible for the most neurotoxic effects associated with the disease. Strategies to ameliorate the toxicity of these intermediate Aβ42 oligomeric species include the use of short, Aβ42-interacting peptides that either inhibit the formation of the Aβ42 oligomeric species or promote their conversion to high-molecular-weight aggregates. We therefore designed such an Aβ42interacting peptide that is based on the β-hairpin amino acid sequence of the APPI, which exhibits high similarity to the β-sheet-like aggregation site of Aβ42. Upon tight binding of this 20-mer cyclic peptide to Aβ42 (in a 1:1 molar ratio), the formation of Aβ42 aggregates was enhanced, and consequently, Aβ42-mediated cell toxicity was ameliorated. We showed that in the presence of the cyclic peptide, interactions of Aβ42 with both plasma and mitochondrial membranes and with phospholipid vesicles that mimic these membranes were inhibited. Specifically, the cyclic peptide inhibited Aβ42-mediated mitochondrial membrane depolarization and reduced Aβ42-mediated apoptosis and cell death. We suggest that the cyclic peptide modulates Aβ42 aggregation by enhancing the formation of large aggregates�as opposed to low-molecular-weight intermediates� and as such has the potential for further development as an AD therapeutic.

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Section: Introductionmentioning

confidence: 99%

APPI-Derived Cyclic Peptide Enhances Aβ42 Aggregation and Reduces Aβ42-Mediated Membrane Destabilization and Cytotoxicity

Lacham-Hartman,

Moshe,

Ben-Zichri

et al. 2023

ACS Chem. Neurosci.

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A label-free high-throughput protein solubility assay and its application to Aβ40

Lindberg,

Axell,

Sparr

et al. 2024

Biophysical Chemistry

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Branched Amphiphilic Polylactides as a Polymer Matrix Component for Biodegradable Implants

et al. 2023

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The combination of biocompatibility, biodegradability, and high mechanical strength has provided a steady growth in interest in the synthesis and application of lactic acid-based polyesters for the creation of implants. On the other hand, the hydrophobicity of polylactide limits the possibilities of its use in biomedical fields. The ring-opening polymerization of L-lactide, catalyzed by tin (II) 2-ethylhexanoate in the presence of 2,2-bis(hydroxymethyl)propionic acid, and an ester of polyethylene glycol monomethyl ester and 2,2-bis(hydroxymethyl)propionic acid accompanied by the introduction of a pool of hydrophilic groups, that reduce the contact angle, were considered. The structures of the synthesized amphiphilic branched pegylated copolylactides were characterized by 1H NMR spectroscopy and gel permeation chromatography. The resulting amphiphilic copolylactides, with a narrow MWD (1.14–1.22) and molecular weight of 5000–13,000, were used to prepare interpolymer mixtures with PLLA. Already, with the introduction of 10 wt% branched pegylated copolylactides, PLLA-based films had reduced brittleness, hydrophilicity, with a water contact angle of 71.9–88.5°, and increased water absorption. An additional decrease in the water contact angle, of 66.1°, was achieved by filling the mixed polylactide films with 20 wt% hydroxyapatite, which also led to a moderate decrease in strength and ultimate tensile elongation. At the same time, the PLLA modification did not have a significant effect on the melting point and the glass transition temperature; however, the filling with hydroxyapatite increased the thermal stability.

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Fibril Growth Behavior of Amyloid β on Polymer-Based Planar Membranes: Implications for the Entanglement and Hydration of Polymers

Cited by 3 publications

References 55 publications

APPI-Derived Cyclic Peptide Enhances Aβ42 Aggregation and Reduces Aβ42-Mediated Membrane Destabilization and Cytotoxicity

APPI-Derived Cyclic Peptide Enhances Aβ42 Aggregation and Reduces Aβ42-Mediated Membrane Destabilization and Cytotoxicity

A label-free high-throughput protein solubility assay and its application to Aβ40

Branched Amphiphilic Polylactides as a Polymer Matrix Component for Biodegradable Implants

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