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

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(4), P. 2545 - 2647

Published: Feb. 5, 2021

Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural dynamic characterization all species along pathways from monomers to fibrils challenging by experimental computational means because they involve intrinsically disordered proteins most diseases. Yet understanding how amyloid become toxic challenge developing treatment for these Here we review what computer, vitro, vivo, pharmacological experiments tell us about accumulation deposition oligomers (Aβ, tau), α-synuclein, IAPP, superoxide dismutase 1 proteins, which have been mainstream concept underlying Alzheimer's disease (AD), Parkinson's (PD), type II diabetes (T2D), amyotrophic lateral sclerosis (ALS) research, respectively, years.

Language: Английский

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Half a century of amyloids: past, present and future

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(15), P. 5473 - 5509

Published: Jan. 1, 2020

Amyloid diseases are global epidemics with profound health, social and economic implications yet remain without a cure. This dire situation calls for research into the origin pathological manifestations of amyloidosis to stimulate continued development new therapeutics. In basic science engineering, cross-β architecture has been constant thread underlying structural characteristics functional amyloids, realizing that amyloid structures can be both in nature fuelled innovations artificial whose use today ranges from water purification 3D printing. At conclusion half century since Eanes Glenner's seminal study amyloids humans, this review commemorates occasion by documenting major milestones date, perspectives biology, biophysics, medicine, microbiology, engineering nanotechnology. We also discuss challenges opportunities drive interdisciplinary field moving forward.

Language: Английский

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Inhibition of amyloid beta toxicity in zebrafish with a chaperone-gold nanoparticle dual strategy

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Aug. 22, 2019

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders, yet no major breakthroughs have been made in AD human trials and remains a paramount challenge stigma medicine. Here we eliminate toxicity amyloid beta (Aβ) facile, high-throughput zebrafish (Danio rerio) model using casein coated-gold nanoparticles (βCas AuNPs). βCas AuNPs systemic circulation translocate across blood brain barrier larvae sequester intracerebral Aβ42 its elicited nonspecific, chaperone-like manner. This evidenced by behavioral pathology, reactive oxygen species neuronal dysfunction biomarkers assays, complemented histology inductively coupled plasma-mass spectroscopy. We further demonstrate capacity recovering mobility cognitive function adult exposed to Aβ. potent, safe-to-use, easy-to-apply nanomedicine may find broad use for eradicating toxic proteins implicated range diseases.

Language: Английский

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Protein-Capped Metal Nanoparticles Inhibit Tau Aggregation in Alzheimer’s Disease

ACS Omega, Journal Year: 2019, Volume and Issue: 4(7), P. 12833 - 12840

Published: July 29, 2019

The Alzheimer's disease (AD) therapeutic research is yielding a large number of potent molecules. nanoparticle-based therapeutics against the protein aggregation in AD also taking lead especially with amyloid-β as primary target. In this work, we have screened for first time protein-capped (PC) metal nanoparticles their potency inhibiting Tau vitro. We present novel function PC-Fe3O4 and PC-CdS inhibitors by fluorescence spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electron microscopy. demonstrate that biologically synthesized PC-metal nanoparticles, iron oxide do not affect viability neuroblastoma cells. Moreover, show dual properties inhibition disaggregation Tau. Thus, can take be modified specific drug delivery due to very small size. current work presents unprecedented strategy design anti-Tau drugs, which provides interesting insights understand role biological nanostructures disease.

Language: Английский

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A Biocompatible Second Near-Infrared Nanozyme for Spatiotemporal and Non-Invasive Attenuation of Amyloid Deposition through Scalp and Skull

ACS Nano, Journal Year: 2020, Volume and Issue: 14(8), P. 9894 - 9903

Published: July 27, 2020

Phototherapy, such as photodynamic therapy and photothermal therapy, holds great potential for modulation of Alzheimer's β-amyloid (Aβ) self-assembly. Unfortunately, current works phototherapy disease (AD) are just employing either visible or first near-infrared (NIR-I) light with limited tissue penetration, which can not avoid damaging nearby normal tissues AD patients through the dense skull scalp. To overcome shortcomings phototherapy, herein we report an amyloid targeting, N-doped three-dimensional mesoporous carbon nanosphere (KD8@N-MCNs) a second (NIR-II) PTT agent. This makes it possible dissociation Aβ aggregates scalp in NIR-II window without hurting tissues. Besides, KD8@N-MCNs have both superoxide dismutase catalase activities, scavenge intracellular superfluous reactive oxygen species alleviate neuroinflammation vivo. Furthermore, efficiently cross blood–brain barrier owing to covalently grafted target peptides KLVFFAED on surface. In vivo studies demonstrate that decrease deposits, ameliorate memory deficits, 3xTg-AD mouse model. Our work provides biocompatible non-invasive way attenuate AD-associated pathology.

Language: Английский

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Nanomaterials for the treatment and diagnosis of Alzheimer's disease: An overview

NanoImpact, Journal Year: 2020, Volume and Issue: 20, P. 100251 - 100251

Published: Aug. 31, 2020

Language: Английский

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Application of carbon nano onions in the biomedical field: recent advances and challenges

Biomaterials Science, Journal Year: 2020, Volume and Issue: 9(3), P. 626 - 644

Published: Nov. 10, 2020

Carbon nano onions (CNOs) are carbonaceous nanostructures composed of multiple concentric shells fullerenes. These cage-within-cage structures remain as one the most exciting and fascinating carbon forms, along with graphene its derivatives, due to their unique chemical physical properties. Their exceptional biocompatibility biosafety make them an attractive choice in a wide range areas, including biological systems. This nanomaterial displays low toxicity, high dispersity aqueous solutions (upon surface functionalization), pharmaceutical efficiency. Even though CNOs were discovered almost simultaneously nanotubes (CNTs), potential biomedical applications still appears unrealized. The existence is equally important, just like any other such CNTs fullerenes, because they display ability form another nanostructure wonderful Therefore, this mini-review summarizes recent studies geared towards developing for various applications, sensing, drug delivery, imaging, tissue engineering, therapeutic drug. It concludes by discussing nanomaterial.

Language: Английский

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NIR‐II Hydrogen‐Bonded Organic Frameworks (HOFs) Used for Target‐Specific Amyloid‐β Photooxygenation in an Alzheimer's Disease Model

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(2)

Published: Nov. 4, 2021

Abstract Phototherapy has emerged as a powerful approach for interrupting β‐amyloid (Aβ) self‐assembly. However, deeper tissue penetration and safer photosensitizers are urgent to be exploited avoiding damaging nearby normal tissues improving therapeutic effectiveness. A hydrogen‐bonded organic framework (HOF)‐based NIR‐II photooxygenation catalyst is presented here settle the abovementioned challenges. By encapsulating pyridinium hemicyanine dye DSM with large two‐photon absorption (TPA) cross‐section in window into porphyrin‐based HOF, resultant DSM@n‐HOF‐6 exhibits significant NIR‐II‐excited Fluorescence Resonance Energy Transfer (FRET) generate singlet oxygen ( 1 O 2 ) Aβ oxidation. Further, target peptides of KLVFFAED (KD8) covalently grafted on enhance blood–brain barrier (BBB) permeability selectivity. The HOF‐based shows an outstanding inhibitory effect aggregation upon irradiation. Further vivo studies demonstrate obvious decrease craniocerebral plaques recovery memory deficits triple‐transgenic AD (3×Tg‐AD) model mice.

Language: Английский

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Graphene Quantum Dots as Flourishing Nanomaterials for Bio-Imaging, Therapy Development, and Micro-Supercapacitors

Micromachines, Journal Year: 2020, Volume and Issue: 11(9), P. 866 - 866

Published: Sept. 18, 2020

Graphene quantum dots (GQDs) are considerably a new member of the carbon family and shine amongst other members, thanks to their superior electrochemical, optical, structural properties as well biocompatibility features that enable us engage them in various bioengineering purposes. Especially, confinement edge effects giving GQDs tremendous character, while heteroatom doping attributes specifically meritoriously tune prospective characteristics for innumerable operations. Considering substantial role offered by area biomedicine nanoscience, through this review paper, we primarily focus on applications bio-imaging, micro-supercapacitors, therapy development. The size-dependent aspects, functionalization, particular utilization discussed detail with respect distinct nano-bio-technological applications.

Language: Английский

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The role of surfaces on amyloid formation

Biophysical Chemistry, Journal Year: 2021, Volume and Issue: 270, P. 106533 - 106533

Published: Jan. 30, 2021

Interfaces can strongly accelerate or inhibit protein aggregation, destabilizing proteins that are stable in solution or, conversely, stabilizing aggregation-prone. Although this behaviour is well-known, our understanding of the molecular mechanisms underlying surface-induced aggregation still largely incomplete. A major challenge represented by high number physico-chemical parameters involved, which highly specific to considered combination protein, surface properties, and conditions. The key aspect determining role interfaces relative propensity aggregate at with respect bulk. In review, we discuss multiple determinants regulate balance. We summarize current experimental techniques aimed characterizing interfaces, highlight need complement analysis theoretical modelling. particular, illustrate how chemical kinetic be combined methods provide insights into under both stagnant agitation recent progress study important amyloids systems, focusing on selected relevant interfaces.

Language: Английский

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