Congo Red Inhibits Proteoglycan and Serum Amyloid P Binding to Amyloid β Fibrils

Gupta-Bansal, Rekha; Brunden, Kurt R.

doi:10.1046/j.1471-4159.1998.70010292.x

Cited by 21 publications

(11 citation statements)

References 35 publications

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“…After 24 h of incubation, soluble A␤ was separated from aggregated and fibrillar peptide by centrifugation (23,24). Different chondroitin sulfate-derived saccharides had variable effects on the amount of pelletable aggregates detected with greater effects seen for A␤42 (Fig.…”

Section: Induction and Morphology Of A␤ Fibril In The Presence Ofmentioning

confidence: 99%

“…The GAG binding site on the A␤ peptide has been investigated using amino acid substitution of the A␤1-28 peptide and as a function of aggregation state (22,23). These studies have demonstrated that although electrostatic interactions through basic amino acids contribute to GAG binding, nonionic interactions, such as hydrogen bonding and van der Waals packing, play a role in GAG-induced A␤ folding and aggregation (22).…”

mentioning

confidence: 99%

“…These studies have demonstrated that although electrostatic interactions through basic amino acids contribute to GAG binding, nonionic interactions, such as hydrogen bonding and van der Waals packing, play a role in GAG-induced A␤ folding and aggregation (22). Furthermore, GAG-A␤ interactions are more sensitive to the conformation and aggregation state of A␤ rather than the primary sequence (22,23). Together these results suggested that inhibition of A␤-GAG interactions through targeting of the GAG binding site on A␤ may not provide a viable therapeutic.…”

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confidence: 99%

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Amyloid-β Interactions with Chondroitin Sulfate-derived Monosaccharides and Disaccharides

Fraser

Darabie²,

McLaurin

2001

Journal of Biological Chemistry

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In Alzheimer's disease, the major pathological features are diffuse and senile plaques that are primarily composed of the amyloid-␤ (A␤) peptide. It has been proposed that proteoglycans and glycosaminoglycans (GAG) facilitate amyloid fibril formation and/or stabilize the plaque aggregates. To develop effective therapeutics based on A␤-GAG interactions, understanding the A␤ binding motif on the GAG chain is imperative. Using electron microscopy, fluorescence spectroscopy, and competitive inhibition ELISAs, we have evaluated the ability of chondroitin sulfate-derived monosaccharides and disaccharides to induce the structural changes in A␤ that are associated with GAG interactions. Our results demonstrate that the disaccharides GalNAc-4-sulfate(4S), ⌬UA-GalNAc-6-sulfate(6S), and ⌬UA-GalNAc-4,6-sulfate(4S,6S), the iduronic acid-2-sul-

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Section: Induction and Morphology Of A␤ Fibril In The Presence Ofmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Amyloid-β Interactions with Chondroitin Sulfate-derived Monosaccharides and Disaccharides

Fraser

Darabie²,

McLaurin

2001

Journal of Biological Chemistry

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“…This mutually disadvantageous interaction holds the amyloid components in a trap and strengthens the amyloid generating and stabilizing process which eventually leads to widespread neuronal loss. The inhibition of the bond between SAP and Aβ results in free SAP and Aβ can be proteolytically cleaved and cleared from the brain [28,29,63]. Free SAP can be removed from the CNS by the active effl ux transport demonstrated here.…”

Section: Discussionmentioning

confidence: 77%

Efflux transport of serum amyloid P component at the blood-brain barrier

Veszelka¹,

Laszy²,

Pazmany³

et al. 2013

European Journal of Microbiology and Immunology

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Serum amyloid P component (SAP), a member of the innate immune system, does not penetrate the brain in physiological conditions; however, SAP is a stabilizing component of the amyloid plaques in neurodegenerative diseases. We investigated the cerebrovascular transport of human SAP in animal experiments and in culture blood-brain barrier (BBB) models. After intravenous injection, no SAP could be detected by immunohistochemistry or ELISA in healthy rat brains. Salmonella typhimurium lipopolysaccharide injection increased BBB permeability for SAP and the number of cerebral vessels labeled with fluorescein isothiocyanate (FITC)-SAP in mice. Furthermore, when SAP was injected to the rat hippocampus, a time-dependent decrease in brain concentration was seen demonstrating a rapid SAP efflux transport in vivo. A temperature-dependent bidirectional transport of FITC-SAP was observed in rat brain endothelial monolayers. The permeability coefficient for FITC-SAP was significantly higher in abluminal to luminal (brain to blood) than in the opposite direction. The luminal release of FITC-SAP from loaded endothelial cells was also significantly higher than the abluminal one. Our data indicate the presence of BBB efflux transport mechanisms protecting the brain from SAP penetration. Damaged BBB integrity due to pathological insults may increase brain SAP concentration contributing to development of neurodegenerative diseases.

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“…olfactory neuroblasts) remains to be an issue. Congo red, which is known to stain amyloid deposits for several decades [216][217][218], stimulated the ongoing search for small markers of Aβ levels. Yet, the detailed mechanism of Congo red binding is still a subject of investigations [219][220][221][222][223][224].…”

Section: Diagnostics -Markers For Admentioning

confidence: 99%

Drug Development and PET-Diagnostics for Alzheimers Disease

Schmidt¹,

Braun²,

Narlawar

2005

CMC

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The exact cause of Alzheimer's disease is still unknown; despite the dramatic progress in understanding. Most gene mutations associated with Alzheimer's disease point to the amyloid precursor protein and amyloid beta. The alpha-, beta- and gamma-secretases are the three executioners of amyloid precursor protein processing. Significant progress has been made in the selective inhibition of these proteases, regardless of the availability of structural information. Several peptidic and non-peptidic leads were identified and first drug candidates are in clinical trials. Cholesterol lowering drugs and metal chelators are also in advanced clinical stages as disease modifiers. Successful trials demand either large cohorts or reliable markers for Alzheimer's disease. Therefore, several radiomarkers are under investigation to support such clinical trials.

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Congo Red Inhibits Proteoglycan and Serum Amyloid P Binding to Amyloid β Fibrils

Abstract: Various data suggest that Alzheimer's disease results from the accumulation of amyloid /3 (Aj3) peptide fibrils and the consequent formation of senile plaques in the cognitive regions of the brain.

Cited by 21 publications

References 35 publications

Amyloid-β Interactions with Chondroitin Sulfate-derived Monosaccharides and Disaccharides

Amyloid-β Interactions with Chondroitin Sulfate-derived Monosaccharides and Disaccharides

Efflux transport of serum amyloid P component at the blood-brain barrier

Drug Development and PET-Diagnostics for Alzheimers Disease

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