Efficient Modulation of β-Amyloid Peptide Fibrillation with Polymer Nanoparticles Revealed by Super-Resolution Optical Microscopy

Ye, Zhongju; Wei, Lin; Li, Yiliang; Xiao, Lehui

doi:10.1021/acs.analchem.9b01877

Cited by 31 publications

(29 citation statements)

References 50 publications

(109 reference statements)

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“…927 Cationic fluorescent conjugated polymer nanoparticles are shown to inhibit Aβ aggregation. 928 Nanoliposomes decorated with Aβ binding surface containing benzothiazolyl are proposed to be an effective therapeutic systems for AD treatment. 929 For other peptide-based inhibitors, readers are referred to a recent review 930 and recent articles.…”

Section: Polymer-based Moleculesmentioning

confidence: 99%

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

et al. 2021

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Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D) and amyotrophic lateral sclerosis (ALS) research, respectively for over many years.While SOD1 is a globular protein with a well-defined 3D structure, the Aβ, tau and α-synuclein proteins belong to the class of intrinsically disordered proteins (IDPs). IDPs are also known to play a critical role in many cellular functions such as signal transduction, cell growth, binding with DNA and RNA, and transcription, and are implicated in the development of cardiovascular problems and cancers 29 . The IDPs involved in neurodegenerative diseases have a few aggregation-prone regions and overall all IDPs have a low mean hydrophobicity and a high mean net charge 30 .IDPs are structurally flexible and lack stable secondary structures in aqueous solution. When isolated, they behave as polymers in a good solvent and their radii of gyration are well described by the Flory scaling law. 31 The insolubility and high self-assembly propensity of IDPs implicated in degenerative diseases have prevented high-resolution structural determination by solution nuclear magnetic resolution (NMR) and X-ray diffraction experiments. Local information at all aggregation steps can be, however, obtained by chemical shifts, residual coupling constants, and J-couplings from NMR, exchange hydrogen/deuterium (H/D) NMR, Raman spectroscopy; and secondary structure from fast Fourier infrared spectroscopy (FTIR) or circular dichroism (CD). Long-range tertiary contacts can be deduced from paramagnetic relaxation enhancement (PRE) NMR spectroscopy and single molecule Förster resonance energy transfer (sm-FRET), and short-range distance contacts can be extracted by cross linked residues determined by mass spectrometry (MS). Low-resolution 3D information of monomers and oligomers can be obtained by ion-mobility mass-spectrometry data (IM/MS) providing cross-collision sections, dynamic light scattering (DLS), pulse field gradient NMR spectroscopy and fluorescence correlation spectroscopy (FCS) providing hydrodynamics radius, small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), atomic force microscopy (AFM) and transmission electron microscopy (TEM) providing height features of the aggregates, as reported by some o...

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Section: Polymer-based Moleculesmentioning

confidence: 99%

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

et al. 2021

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“…The positively charged fluorescent conjugated polymer NPs (CPNPs) were prepared to inhibit Aβ 1–40 peptide fibrillation ( Figure 14 B) [ 188 ]. Moreover, CPNPs with excellent photophysical properties provided fluorescence signals for probing the interaction with Aβ peptides.…”

Section: Nanomaterialsmentioning

confidence: 99%

“…( B ) Schematic diagram of the procedures for CPNPs fabrication and Aβ 1–40 fibril inhibition with CPNPs. Reprinted with permission from reference [ 188 ]. Copyright 2019 American Chemical Society.…”

Section: Figures and Schemementioning

confidence: 99%

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

et al. 2021

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The aberrant aggregation of amyloid-β (Aβ) peptides in the brain has been recognized as the major hallmark of Alzheimer’s disease (AD). Thus, the inhibition and dissociation of Aβ aggregation are believed to be effective therapeutic strategiesforthe prevention and treatment of AD. When integrated with traditional agents and biomolecules, nanomaterials can overcome their intrinsic shortcomings and boost their efficiency via synergistic effects. This article provides an overview of recent efforts to utilize nanomaterials with superior properties to propose effective platforms for AD treatment. The underlying mechanismsthat are involved in modulating Aβ aggregation are discussed. The summary of nanomaterials-based modulation of Aβ aggregation may help researchers to understand the critical roles in therapeutic agents and provide new insight into the exploration of more promising anti-amyloid agents and tactics in AD theranostics.

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“…Lipid-stabilized pores are mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers 2016, 2020 [196] Aβ40, Aβ42 HEK293 cells Ile41-Ala42 residues in Aβ42.…”

Section: In Silico Studiesmentioning

confidence: 99%

The Membrane Axis of Alzheimer's Nanomedicine

Tang

Andrikopoulos

et al. 2020

Advanced NanoBiomed Research

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Alzheimer's disease (AD) is a major neurological disorder impairing its carrier's cognitive function, memory, and lifespan. While the development of AD nanomedicine is still nascent, the field is evolving into a new scientific frontier driven by the diverse physicochemical properties and theranostic potential of nanomaterials and nanocomposites. Characteristic to the AD pathology is the deposition of amyloid plaques and tangles of amyloid beta (Aβ) and tau, whose aggregation kinetics may be curbed by nanoparticle inhibitors via sequence‐specific targeting or nonspecific interactions with the amyloidogenic proteins. As literature implicates cell membrane as a culprit in AD pathogenesis, herein, the membrane axis of AD nanomedicine is summarized and a new rationale that the field development may greatly benefit from harnessing our existing knowledge of Aβ‐membrane interaction, nanoparticle–membrane interaction, and Aβ–nanoparticle interaction is presented.

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Efficient Modulation of β-Amyloid Peptide Fibrillation with Polymer Nanoparticles Revealed by Super-Resolution Optical Microscopy

Cited by 31 publications

References 50 publications

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Nanomaterials for Modulating the Aggregation of β-Amyloid Peptides

The Membrane Axis of Alzheimer's Nanomedicine

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