Congo Red protects against toxicity of β-amyloid peptides on rat hippocampal neurones

Burgevin, Marie-Claude; Passat, Marylène; Daniel, Nadine; Capet, Marc; Doble, Adam

doi:10.1097/00001756-199412000-00006

Cited by 47 publications

(38 citation statements)

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“…The inhibition of channel formation by Congo Red is consistent with biological findings that Congo Red prevented toxic effects of A␤ on red blood cells (21) and cultured neurons (36,37). The requirement for anionic lipids for channel formation is relevant to the finding that phospholipids of neural membranes from AD brains contain significantly higher levels of phosphatidylserine (PS) than normal brains (38).…”

Section: Role Of Aggregationsupporting

confidence: 78%

Alzheimer amyloid aβ1-42 channels: Effects of solvent, pH, and congo red

1999

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Substantial genetic and biochemical evidence implicates amyloid peptides (Abeta) in the etiology of Alzheimer's Disease (AD). Recent evidence indicates that Abeta1-42 is the predominant species in the hallmark senile amyloid plaque of AD. Furthermore, Abeta1-42 forms aggregates inside lysosomes of cultured neurons leading to lysosomal disruption and cell death. We report here that Abeta1-42 forms slightly cation selective, voltage-independent ion channels with multiple conductance levels at neurotoxic concentrations in planar bilayer membranes. The channels show substantial irregularity of activity, and the size of conductances and the length of open lifetimes depend on solvent history. Formation of channels requires anionic lipids, is enhanced in acidic solutions, and is inhibited by Congo Red. These properties suggest that the channels are formed by aggregates of Abeta1-42. In addition, the channels are reversibly blocked by zinc in a voltage-independent manner. The properties of these channels would likely render them neurotoxic to relevant neurons in vivo. These results are consistent with the channel hypothesis of Abeta neurotoxicity.

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Section: Role Of Aggregationsupporting

confidence: 78%

Alzheimer amyloid aβ1-42 channels: Effects of solvent, pH, and congo red

1999

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“…Interestingly, emerging studies demon- [4,9] . It has been reported that congo red is able to block Aβ aggregation and toxicity in rat hippocampal neuron culture [20] , HeLa and PC12 cells and in human macrophage culture [21,22] . In addition, congo red can inhibit amyloid toxicity by the blockade of Ca 2+ permeable amyloid-formed ion channels [6,7] .…”

Section: Discussionmentioning

confidence: 99%

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

et al. 2014

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Aim: Congo red, a secondary diazo dye, is usually used as an indicator for the presence of amyloid fibrils. Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, we investigated the effects of congo red on ACh-induced Ca 2+ oscillations in mouse pancreatic acinar cells in vitro. Methods: Acutely dissociated pancreatic acinar cells of mice were prepared. A U-tube drug application system was used to deliver drugs into the bath. Intracellular Ca 2+ oscillations were monitored by whole-cell recording of Ca 2+ -activated Cl -currents and by using confocal Ca 2+ imaging. For intracellular drug application, the drug was added in pipette solution and diffused into cell after the wholecell configuration was established. Results: Bath application of ACh (10 nmol/L) induced typical Ca 2+ oscillations in dissociated pancreatic acinar cells. Addition of congo red (1, 10, 100 µmol/L) dose-dependently enhanced Ach-induced Ca 2+ oscillations, but congo red alone did not induce any detectable response. Furthermore, this enhancement depended on the concentrations of ACh: congo red markedly enhanced the Ca 2+ oscillations induced by ACh (10-30 nmol/L), but did not alter the Ca 2+ oscillations induced by ACh (100-10000 nmol/L). Congo red also enhanced the Ca 2+ oscillations induced by bath application of IP 3 (30 µmol/L). Intracellular application of congo red failed to alter ACh-induced Ca 2+ oscillations. Conclusion: Congo red significantly modulates intracellular Ca 2+ signaling in pancreatic acinar cells, and this pharmacological effect should be fully considered when developing congo red as a novel therapeutic drug.

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“…Our observation that Congo red stabilizes hA at the oligomer level is particularly interesting in light of the current view that distinct amyloid oligomers rather than the polymorphic fibrils are the toxic agent. The situation may, however, be more complex as Congo red has also been reported to inhibit hA cytotoxicity and membrane activity (13,30,39,40) AFM is unique in its ability to image dynamic processes at the nanometer scale and in real time under physiological buffer conditions. One perceived drawback is that fibril growth may be constrained by the mica surface.…”

Section: Discussionmentioning

confidence: 99%

Human Amylin Oligomer Growth and Fibril Elongation Define Two Distinct Phases in Amyloid Formation

Green

Goldsbury²,

Kistler

et al. 2004

Journal of Biological Chemistry

145

125

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Human amylin (hA), a 37-amino-acid polypeptide, is one of a number of peptides with the ability to form amyloid fibrils and cause disease. It is the main constituent of the pancreatic amyloid deposits associated with type 2 diabetes. Increasing interest in early assembly intermediates rather than the mature fibrils as the cytotoxic agent has led to this study in which the smallest hA oligomers have been captured by atomic force microscopy. These are 2.3 ؎ 1.9 nm in height, 23 ؎ 14 nm in length, and consist of an estimated 16 hA molecules. Oligomers first grow to a height of about 6 nm before they begin to significantly elongate into fibrils. Congo red inhibits elongation but not the growth in height of hA oligomers. Two distinct phases have thus been identified in hA fibrillogenesis: lateral growth of oligomers followed by longitudinal growth into mature fibrils. These observations suggest that mature fibrils are assembled directly via longitudinal growth of full-width oligomers, making assembly by lateral association of protofibrils appear less likely.

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Congo Red protects against toxicity of β-amyloid peptides on rat hippocampal neurones

Cited by 47 publications

References 0 publications

Alzheimer amyloid aβ1-42 channels: Effects of solvent, pH, and congo red

Alzheimer amyloid aβ1-42 channels: Effects of solvent, pH, and congo red

Congo red modulates ACh-induced Ca2+ oscillations in single pancreatic acinar cells of mice

Human Amylin Oligomer Growth and Fibril Elongation Define Two Distinct Phases in Amyloid Formation

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