Graphene oxide sheets and quantum dots inhibit α-synuclein amyloid formation by different mechanisms

Ghaeidamini, Marziyeh; Bernson, David; Sasanian, Nima; Kumar, Ranjeet; Esbjörner, Elin K.

doi:10.1039/d0nr05003b

Cited by 40 publications

(33 citation statements)

References 72 publications

(85 reference statements)

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“…Therefore, GQDs have been suggested as therapeutic agents in inflammatory diseases [26]. GQDs also have protective impacts on Parkinson's disease through interaction with α-synuclein without complications [27,28]. In line with the above studies, our results demonstrated that GQDs-PEG attenuated heart injuries and improved left ventricular contractility and cardiac function after MI.…”

Section: Discussionsupporting

confidence: 87%

PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences

Rostamzadeh

Shadkam-Farrokhi

Jafarinejad-Farsangi

et al. 2021

Oxidative Medicine and Cellular Longevity

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Introduction. The biocompatibility and potential application of graphene-based nanomaterials in biomedicine have been documented. The effects of polyethylene glycol-graphene quantum dots (GQDs-PEG) on cardiac function in rats with myocardial infarction (MI) were examined. Methods. Wistar rats were randomly assigned to two main groups, each consisting of sham-Veh., MI-Veh., and MI+GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending (LAD) coronary artery. After MI, GQDs-PEG were injected at different doses IP every other day for two weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of myocardial MDA (malondialdehyde), SOD (superoxide dismutase), GPX (glutathione peroxidase), and TAC (total antioxidant capacity) were measured by the ELISA method. The serum ALP, ALT, AST, creatinine, and urea levels were measured using the photometric method. The infarct size was assessed by TTC staining. Results. GQDs-PEG decreased the infarct size at doses of 10 and 20 mg/kg and recovered the MI-induced reductions of +dp/dt max and -dp/dt max in the study groups. GQDs-PEG normalized systolic blood pressure and left ventricular systolic pressure reduction at the dose of 20 mg/kg in the MI group. Heart SOD, GPX, and TAC increased in the GQDs-PEG 10 and 20 groups. Almost no signs of toxic effects due to GQDs-PEG administration were observed on the liver and kidneys. Conclusions. The results provided clear evidence that GQDs-PEG improve cardiac performance and hemodynamic parameters in rats with MI by reducing oxidative stress. GQDs-PEG is proposed as a therapeutic target for the treatment of MI.

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Section: Discussionsupporting

confidence: 87%

PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences

Rostamzadeh

Shadkam-Farrokhi

Jafarinejad-Farsangi

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Recent studies have shown that GDQs themselves can also inhibit α-syn aggregation and promote disaggregation of mature fibrils ( Mohammad-Beigi et al, 2019 ). This aggregation inhibitory effect of GDQs is dependent on its surface chemistry and dimensionality, which can interfere with the rate of protein aggregation, the mechanism of inhibition, and the morphology of the aggregated products ( Ghaeidamini et al, 2020 ). The effect of GDQs was further illustrated by Kim et al (2018) .…”

Section: Promising Theranostics Nanotechnology Targeting α-Syn Aggregationmentioning

confidence: 99%

Parkinson’s Disease: A Nanotheranostic Approach Targeting Alpha-Synuclein Aggregation

Zoey

Palanivel

Gulyás

2021

Front. Cell Dev. Biol.

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Parkinson’s disease (PD) is one of the most common neurodegenerative disorders that is implicated in aging populations. As numerous developed nations are experiencing progressively aging populations today, there is a heightened propensity for the occurrence of PD cases. Alpha-synuclein (α-syn) aggregation has been considered to be the pivotal mechanism leading to PD pathogenesis. Thus, early diagnostic and therapeutic strategies targeting the misfolded α-syn protein can potentially improve the prognosis of PD. With rapid advancements in nanotechnology in the last decade, effective solutions to various neurodegenerative and oncological diseases have been suggested. This review will explore the current innovations in nanotechnology that target the α-syn aggregation pathway, and reinstate the promise they hold as effective early diagnostic and therapeutic solutions to PD.

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“…More specifically, graphene sheets sequester the α‐synuclein monomers, preventing primary nucleation and elongation, whereas GQDs affect the secondary formation processes. [ 88 ] Of note, the α‐synuclein aggregation inhibition is time‐ and concentration‐dependent [ 88,90 ] with low concentration to potentially enhance the aggregation phenomena. [ 88 ] In addition to the aggregation inhibition, GQDs have been shown to reduce the number of Lewy bodies and the subsequent Lewy neurite formation, bringing to inhibition of neuronal death and synaptic loss.…”

Section: Gbms In Neurodegenerative Diseasesmentioning

confidence: 99%

“…As in AD, the main therapeutic approaches for PD focus on the dissociation of formed fibrils or the fibrillation inhibition of αsynuclein. [87] To achieve this therapeutic effect, graphene sheets [88,89] and GQDs have been used. [88][89][90] These reported studies have shown that the electrostatic interactions between the negatively charged surfaces of the GBMs and the positively charged regions of α-synuclein are mainly responsible for the dissociation and the formation inhibition of fibrils.…”

Section: Graphene-based Therapeutics For Pdmentioning

confidence: 99%

“…[88] Of note, the α-synuclein aggregation inhibition is time-and concentration-dependent [88,90] with low concentration to potentially enhance the aggregation phenomena. [88] In addition to the aggregation inhibition, GQDs have been shown to reduce the number of Lewy bodies and the subsequent Lewy neurite formation, bringing to inhibition of neuronal death and synaptic loss. [90] Alternative approaches have suggested PD treatment through electrical [91] and photothermal stimulation.…”

Section: Graphene-based Therapeutics For Pdmentioning

confidence: 99%

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Graphene‐Based Nanotechnology in Neurodegenerative Disorders

Tapeinos

2021

Advanced NanoBiomed Research

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Graphene‐based materials (GBMs) demonstrate unique electrochemical, mechanical, thermal, and optical properties rendering them attractive candidates for numerous biomedical applications. Since graphene's discovery, GBMs have been at the forefront of biomedical research offering innovative solutions for numerous diseases, including neurodegenerative disorders (NDs). There are numerous reviews in which synthesis and functionalization methods of GBMs are discussed. However, this review focuses specifically on the recent research advances of GBMs for NDs, and more specifically, on sensing and therapeutic applications. After a short description of NDs’ main characteristics, significant attention is given to the functionalization strategies used to improve the biomedical properties of GBMs, and recent applications for Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. A description of the use of GBMs and neural stem cell technology and known toxicity issues, followed by several limitations that current GBMs need to overcome, completes this review.

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Graphene oxide sheets and quantum dots inhibit α-synuclein amyloid formation by different mechanisms

Abstract: Aggregation and amyloid formation of the 140-residue presynaptic and intrinsically disordered protein α-synuclein (α-syn) is a pathological hallmark of Parkinson's disease (PD). Understanding how α-syn forms amyloid fibrils, and investigations...

Cited by 40 publications

References 72 publications

PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences

PEGylated Graphene Quantum Dot Improved Cardiac Function in Rats with Myocardial Infarction: Morphological, Oxidative Stress, and Toxicological Evidences

Parkinson’s Disease: A Nanotheranostic Approach Targeting Alpha-Synuclein Aggregation

Graphene‐Based Nanotechnology in Neurodegenerative Disorders

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