Heparin nanoparticles for β amyloid binding and mitigation of β amyloid associated cytotoxicity

Wang, Peng; Kouyoumdjian, Hovig; Zhu, David C.; Huang, Xuefei

doi:10.1016/j.carres.2014.07.020

Cited by 20 publications

(8 citation statements)

References 35 publications

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“…This condition seems to be satisfied in most reported cases but in some publications, the ThT detection of heparin-induced amyloid fibrillation was made in pure water. 56,57 Accordingly, care must be taken for the consideration of the fluorescence data obtained in such experiments. It should also be noted that additional amyloid-sensing probes used in the laboratory practice having a basic or a cationic character may also form electrostatic/H-bonded complexes with sulfated GAGs.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Mind Your Dye: The Amyloid Sensor Thioflavin T Interacts with Sulfated Glycosaminoglycans Used To Induce Cross-β-Sheet Motifs

2020

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Thioflavin T (ThT) is a commonly employed fluorescence probe for sensing amyloid fibrils. These highly ordered, insoluble nanostructures colocalize with sulfated glycosaminoglycans (GAGs) being abundant in the extracellular matrix and on the outer surface of cell membranes. To elucidate the positive impact of GAGs on amyloidogenesis, they are frequently used to promote fibril formation in vitro, which is detected by the enhanced fluorescence of ThT. The polyanionic nature and the affinity of GAGs to basic compounds predict that cationic ThT molecules may also bind to them, in addition to cross-β-structures formed in the reaction medium. By means of circular dichroism (CD) and absorption spectroscopy, this study examined the heparin and chondroitin sulfate binding of ThT. The large blue shift of the absorption peak indicated a card-pack type oligomerization of the dye molecules along the linear GAG chains. The strong exciton couplet observed in the CD spectra implies the left-handed, helical arrangement of GAG-associated oligomers of the dye. The decisive contribution of ionic forces for the binding was illustrated by sodium-ion-provoked dissociation of dye−GAG complexes. In silico analysis was performed to complement the experimental findings and to contribute to the understanding of potential molecular mechanisms underlying ThT−GAG interactions. ThT can be considered as an inert component in GAG-induced amyloid assays but only if the experiments are correctly designed.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Mind Your Dye: The Amyloid Sensor Thioflavin T Interacts with Sulfated Glycosaminoglycans Used To Induce Cross-β-Sheet Motifs

2020

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“…However, this property could be very useful in AD therapy. Wang et al have studied this property using magnetic nanoparticles (SPION) coated with heparin and showed concurrent binding with Aβ peptides by a variety of techniques, including enzyme-linked immunosorbent assay, gel electrophoresis, and thioflavin T assay [ 26 ]. Moreover, they observed that these nanoparticles were capable of protecting neuronal cells from Aβ toxicity, demonstrating that this nanosystem could be very promising [ 26 ].…”

Section: Active Targeted Brain Deliverymentioning

confidence: 99%

Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?

Pinheiro

Coutinho

Pinheiro

et al. 2021

IJMS

135

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The blood–brain barrier (BBB) is a barrier that separates the blood from the brain tissue and possesses unique characteristics that make the delivery of drugs to the brain a great challenge. To achieve this purpose, it is necessary to design strategies to allow BBB passage, in order to reach the brain and target the desired anatomic region. The use of nanomedicine has great potential to overcome this problem, since one can modify nanoparticles with strategic molecules that can interact with the BBB and induce uptake through the brain endothelial cells and consequently reach the brain tissue. This review addresses the potential of nanomedicines to treat neurological diseases by using nanoparticles specially developed to cross the BBB.

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“…HS and heparin (HS with higher levels of sulfations and iduronic acid) can have potential beneficial effects on AD patients . In clinical studies, administration of heparin like compounds has been shown to relieve behavioral symptoms in animal models of Alzheimer disease as well as in multi-infarct dementia human patients, although these compounds cannot be used directly for AD treatment due to concerns of potential bleeding side effects associated with anticoagulant activities of native heparin. − HS mimics or nanoparticles can help mitigate cytotoxic Aβ species, , providing exciting leads for AD detection and therapy.…”

mentioning

confidence: 99%

Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides

Wang¹,

Zhao

Nasr³

et al. 2021

ACS Chem. Biol.

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Heparan sulfate (HS) can play important roles in the biology and pathology of amyloid β (Aβ), a hallmark of Alzheimer's disease. To better understand the structure−activity relationship of HS/Aβ interactions, synthetic HS oligosaccharides ranging from tetrasaccharides to decasaccharides have been utilized to study Aβ interactions. Surface plasmon resonance experiments showed that the highly sulfated HS tetrasaccharides bearing full 2-O, 6-O, and N-sulfations exhibited the strongest binding with Aβ among the tetrasaccharides investigated. Elongating the glycan length to hexa-and deca-saccharides significantly enhanced Aβ affinity compared to the corresponding HS tetrasaccharide. Solid state NMR studies of the complexes of Aβ with HS hexa-and deca-saccharides showed most significant chemical shift perturbation in the C-terminus residues of Aβ. The strong binding HS oligosaccharides could reduce the cellular toxicities induced by Aβ. This study provides new insights into HS/Aβ interactions, highlighting how synthetic structurally well-defined HS oligosaccharides can assist in biological understanding of Aβ.

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Heparin nanoparticles for β amyloid binding and mitigation of β amyloid associated cytotoxicity

Cited by 20 publications

References 35 publications

Mind Your Dye: The Amyloid Sensor Thioflavin T Interacts with Sulfated Glycosaminoglycans Used To Induce Cross-β-Sheet Motifs

Mind Your Dye: The Amyloid Sensor Thioflavin T Interacts with Sulfated Glycosaminoglycans Used To Induce Cross-β-Sheet Motifs

Nanoparticles for Targeted Brain Drug Delivery: What Do We Know?

Probing Amyloid β Interactions with Synthetic Heparan Sulfate Oligosaccharides

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