Physical basis of colors seen in Congo red-stained amyloid in polarized light

Howie, Alexander J.; Brewer, D. B.; Howell, D.; Jones, Adrian P.

doi:10.1038/labinvest.3700714

Cited by 145 publications

(144 citation statements)

References 17 publications

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Simple CR staining alone is not definitive for amyloid, but when viewed with polarized light through crossed filters, congophilic amyloid foci cause yellowish apple-green birefringence (Howie et al, 2008). This technique is commonly used to visualize amyloid plaques in situ in post-mortem tissue samples from patients with cerebral amyloid pathologies (Jin et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Functional amyloid formation by Streptococcus mutans

et al. 2012

View full text Add to dashboard Cite

Dental caries is a common infectious disease associated with acidogenic and aciduric bacteria, including Streptococcus mutans. Organisms that cause cavities form recalcitrant biofilms, generate acids from dietary sugars and tolerate acid end products. It has recently been recognized that micro-organisms can produce functional amyloids that are integral to biofilm development. We now show that the S. mutans cell-surface-localized adhesin P1 (antigen I/II, PAc) is an amyloid-forming protein. This conclusion is based on the defining properties of amyloids, including binding by the amyloidophilic dyes Congo red (CR) and Thioflavin T (ThT), visualization of amyloid fibres by transmission electron microscopy and the green birefringent properties of CR-stained protein aggregates when viewed under cross-polarized light. We provide evidence that amyloid is present in human dental plaque and is produced by both laboratory strains and clinical isolates of S. mutans. We provide further evidence that amyloid formation is not limited to P1, since bacterial colonies without this adhesin demonstrate residual green birefringence. However, S. mutans lacking sortase, the transpeptidase enzyme that mediates the covalent linkage of its substrates to the cell-wall peptidoglycan, including P1 and five other proteins, is not birefringent when stained with CR and does not form biofilms. Biofilm formation is inhibited when S. mutans is cultured in the presence of known inhibitors of amyloid fibrillization, including CR, Thioflavin S and epigallocatechin-3-gallate, which also inhibited ThT uptake by S. mutans extracellular proteins. Taken together, these results indicate that S. mutans is an amyloid-forming organism and suggest that amyloidogenesis contributes to biofilm formation by this oral microbe. INTRODUCTIONAmyloid represents a fibrous cross b-sheet quaternary structure comprised of ordered aggregates of peptides or proteins that demonstrate common biophysical properties (Nilsson, 2004). While amyloid formation has been extensively studied in the context of pathological states, for example Alzheimer's disease, the concept of functional amyloid has only recently emerged (Epstein & Chapman, 2008;Fowler et al., 2007;Gebbink et al., 2005;Maury, 2009a;. In bacteria, amyloid formation may be the rule rather than the exception . There are now numerous examples of surface-localized microbial proteins that aggregate and assemble into functional amyloid fibrils.Amyloid fibres have a tensile strength comparable to steel (Smith et al., 2006). The unique physical and morphological properties of amyloid and the fact that it can be formed in a regulated manner suggest that it probably represents a common quaternary structure that is widespread in biology. Therefore, it does not always represent a misfolded protein structure, but instead represents a lowenergy quaternary structure that can occur in the context of function or disease (Fowler et al., 2007). Amyloid is a non-covalent oligomer of extended intermolecular hydrogen-bonded b-sheets that s...

show abstract

Section: Resultsmentioning

confidence: 99%

Functional amyloid formation by Streptococcus mutans

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The first of these dyes was Congo red [335] , whose staining is linked to the presence of the cross-β structure of fibrils. Other amyloid dyes include iodine-sulfuric acid [336] , thioflavin T or S [337] , crystal violet [338] , methyl violet [339] , BTA-1 [340] , chrysamine G [341] , ANS (1-anilinonaphthalene-8-sulfonic acid) [342] , bisANS (4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid) [342] , Nile red [343] , K114 ((trans, trans)-1-bromo-2,5-bis (4-hydroxystyryl) benzene) [344] , FSB [345] , curcumin [346] , nanocurcumin [346] , and others.…”

Section: Amyloid Dyesmentioning

confidence: 99%

Amyloid beta: structure, biology and structure-based therapeutic development

et al. 2017

View full text Add to dashboard Cite

Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β-and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of Aβ. We also discuss the potential receptors that interact with Aβ and mediate Aβ intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on Aβ, its receptors and tau protein, such as small molecules, vaccines and antibodies against Aβ; inhibitors or modulators of β-and γ-secretase; Aβ-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.

show abstract

“…S2) (25,26). Cross-sections of frozen muscle specimens (vastus lateralis and cranial tibial) collected at 3, 9, and 18 months of age from D187N (Ϫ/ϩ) mice ( Fig.…”

Section: D187n (؊/؉) Amyloid Deposition Originates Around Endomysial mentioning

confidence: 99%

Secretion of amyloidogenic gelsolin progressively compromises protein homeostasis leading to the intracellular aggregation of proteins

Page¹,

Suk²,

Bazhenova³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Familial amyloidosis of Finnish type (FAF) is a systemic amyloid disease associated with the deposition of proteolytic fragments of mutant (D187N/Y) plasma gelsolin. We report a mouse model of FAF featuring a muscle-specific promoter to drive D187N gelsolin synthesis. This model recapitulates the aberrant endoproteolytic cascade and the aging-associated extracellular amyloid deposition of FAF. Amyloidogenesis is observed only in tissues synthesizing human D187N gelsolin, despite the presence of full-length D187N gelsolin and its 68-kDa cleavage product in blood-demonstrating the importance of local synthesis in FAF. Loss of muscle strength was progressive in homozygous D187N gelsolin mice. The presence of misfolding-prone D187N gelsolin appears to exacerbate the age-associated decline in cellular protein homeostasis (proteostasis), reflected by the intracellular deposition of numerous proteins, a characteristic of the most common degenerative muscle disease of aging humans, sporadic inclusion body myositis.amyloid ͉ proteostasis ͉ sporadic inclusion body myositis ͉ FAF mouse P rotein homeostasis (proteostasis) refers to the cellular control of the synthesis, structure, trafficking, and degradation of proteins (1). An aging-associated decline in proteostasis capacity may contribute to the onset of many diseases associated with protein misfolding (2-4). Inheriting an aggregation-prone protein(s) further challenges proteostasis capacity upon aging (5). Such challenges can lead to loss-of-function disorders or aggregation-associated degenerative diseases (1-3, 5-9). Whether intracellular and/or extracellular aggregation leads to proteotoxicity in diseases associated with extracellular amyloid, such as Alzheimer's disease, remains unclear (3, 10).Familial amyloidosis of Finnish type (FAF) or gelsolin amyloidosis is thought to result from amyloidogenesis of a fragment of gelsolin causing aging-associated proteotoxicity (1,(11)(12)(13)(14). Plasma gelsolin is a 83-kDa 6-domain Ca 2ϩ -binding protein that is secreted from several cell types into the blood (Ͼ200 g/mL) (15), with muscle contributing significantly (16). A D187 mutation to N or Y (D187N/Y) in plasma gelsolin compromises Ca 2ϩ binding in domain 2 and thus folding (13). This enables aberrant cleavage by furin in the trans-Golgi, generating a 68-kDa fragment (C68) of gelsolin that is secreted (11, 17) (Fig. 1A). Only a fraction of D187N/Y plasma gelsolin in FAF is cleaved by furin; the remainder is secreted as full-length, functional plasma gelsolin. C68 can be further cleaved in the extracellular space by a type I matrix metalloprotease, like MT1-MMP (12), to generate the major (8-kDa) and minor (5-kDa) amyloidogenic fragments that deposit in blood vessel walls, skin, the autonomic nervous system, and the eye of humans, causing cranial and peripheral polyneuropathy, cutis laxa, and corneal lattice dystrophy (18). Deposition also occurs in skeletal and cardiac muscle, leading to cardiomyopathy and muscle weakness (14, 18). Given that human D187N/Y plasma gelso...

show abstract

Physical basis of colors seen in Congo red-stained amyloid in polarized light

Cited by 145 publications

References 17 publications

Functional amyloid formation by Streptococcus mutans

Functional amyloid formation by Streptococcus mutans

Amyloid beta: structure, biology and structure-based therapeutic development

Secretion of amyloidogenic gelsolin progressively compromises protein homeostasis leading to the intracellular aggregation of proteins

Contact Info

Product

Resources

About