Heparan sulphate proteoglycans in Alzheimer's disease and amyloid‐related disorders

Horssen, Jack van; Wesseling, Pieter; Heuvel, L.P.W.J. van den; Waal, R.M.W. de; Verbeek, Marcel M.

doi:10.1016/s1474-4422(03)00484-8

Cited by 196 publications

(157 citation statements)

References 123 publications

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“…Heparan sulfate proteoglycans (HSPGs) have been identified as a codeposited component of amyloid in a number of amyloidogenic diseases (12,13,21,22), and are believed to play a part in the pathology of amyloidogenesis. In this study, our primary question was whether HS is associated with TTR amyloidosis, and if so, what are the potential roles of the polysaccharide in TTR aggregation and amyloidosis?…”

Section: Discussionmentioning

confidence: 99%

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Noborn

O’Callaghan

Hermansson

et al. 2011

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

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Transthyretin (TTR) is a homotetrameric protein that transports thyroxine and retinol. Tetramer destabilization and misfolding of the released monomers result in TTR aggregation, leading to its deposition as amyloid primarily in the heart and peripheral nervous system. Over 100 mutations of TTR have been linked to familial forms of TTR amyloidosis. Considerable effort has been devoted to the study of TTR aggregation of these mutants, although the majority of TTR-related amyloidosis is represented by sporadic cases due to the aggregation and deposition of the otherwise stable wild-type (WT) protein. Heparan sulfate (HS) has been found as a pertinent component in a number of amyloid deposits, suggesting its participation in amyloidogenesis. This study aimed to investigate possible roles of HS in TTR aggregation. Examination of heart tissue from an elderly cardiomyopathic patient revealed substantial accumulation of HS associated with the TTR amyloid deposits. Studies demonstrated that heparin/HS promoted TTR fibrillization through selective interaction with a basic motif of TTR. The importance of HS for TTR fibrillization was illustrated in a cell model; TTR incubated with WT Chinese hamster ovary cells resulted in fibrillization of the protein, but not with HS-deficient cells (pgsD-677). The effect of heparin on TTR fibril formation was further demonstrated in a Drosophila model that overexpresses TTR. Heparin was colocalized with TTR deposits in the head of the flies reared on heparin-supplemented medium, whereas no heparin was detected in the nontreated flies. Heparin of low molecular weight (Klexane) did not demonstrate this effect.systemic amyloidosis | sulfated glycosaminoglycans | aging | heart failure

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Section: Discussionmentioning

confidence: 99%

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Noborn

O’Callaghan

Hermansson

et al. 2011

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

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“…Non-sulfated GAGs include hyaluronic acid, while sulfated GAGs are comprised of chondroitin, keratan, dermatan, and heparan sulfates [Diaz-Nido et al, 2002;van Horssen et al, 2003]. The hypersulfated form of heparan sulfate is referred to as heparin [Diaz-Nido et al, 2002].…”

Section: Glycosaminoglycan Mimeticsmentioning

confidence: 99%

Small molecule inhibitors of Aβ‐aggregation and neurotoxicity

Hawkes

McLaurin

2009

Drug Development Research

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Alzheimer disease (AD) is characterized pathologically by extracellular amyloid deposits composed of Ab peptide, neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau, and a deficit of cholinergic neurons in the basal forebrain. Presently, only symptomatic therapies are available for the treatment of AD and these therapies have a limited time frame of utility. Amyloid disorders represent the effects of chronic Ab production and are not a secondary pathological effect caused by a distant trigger; therefore targeting Ab is a viable pursuit. In this review, we will discuss the various small molecule antiaggregation inhibitors that have been reported in the literature, with emphasis on compounds that are presently being investigated in clinical trials. Drug Dev Res 70 : 111-124, 2009.

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“…It has been reported that several types of saccharide interact with Aβ [17][18][19]. GM1 interacts with Aβ to induce fibril formation [17,18].…”

Section: Interaction Of Saccharides With Amyloid β (1-42)mentioning

confidence: 99%

“…Interestingly, GM1 displays Gal and sialic acid at the nonreducing terminal. In addition, glycosaminoglycans interact with Aβs [19], where 6-sulfo-GlcNAc is an abundant saccharide structure. Therefore, although the saccharide response in SPR analyses was unclear, the obtained binding affinities reflected the in vivo results.…”

Section: Interaction Of Saccharides With Amyloid β (1-42)mentioning

confidence: 99%

“…We particularly focused on the interaction between amyloid β peptide (Aβ) and observed fibril formation on a specific saccharide. It has been reported that the saccharide-protein interaction is related to Alzheimer disease and amyloidosis of Aβ; for example, ganglioside GM1 [17,18] and glycosaminoglycans [19] are related to Aβ amyloidosis. However, no detailed analyses of saccharide-protein interaction associated with amyloidosis of Aβ were conducted.…”

Section: Introductionmentioning

confidence: 99%

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Sugar microarray via click chemistry: molecular recognition with lectins and amyloid β (1–42)

Matsumoto

Yamauchi

Fukuda

et al. 2009

Science and Technology of Advanced Materials

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Sugar microarrays were fabricated on various substrates via click chemistry. Acetylene-terminated substrates were prepared by forming self-assembled monolayers (SAMs) on a gold substrate with alkyl-disulfide and on silicon, quartz and glass substrates with a silane-coupling reagent. The gold substrates were subjected to surface plasmon resonance measurements, and the quartz and glass substrates were subjected to spectroscopy measurements and optical microscopy observation. The saccharide-immobilized substrate on the gold substrate showed specific interaction with the corresponding lectin, and the saccharides showed inert surface properties to other proteins with a high signal-to-noise ratio. We also focused on the saccharide-protein interaction on protein amyloidosis of Alzheimer amyloid β. Amyloid β peptide showed conformation transition on the saccharide-immobilization substrate into a β-sheet, and fibril formation and amyloid aggregates were found on the specific saccharides.

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Heparan sulphate proteoglycans in Alzheimer's disease and amyloid‐related disorders

Cited by 196 publications

References 123 publications

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Heparan sulfate/heparin promotes transthyretin fibrillization through selective binding to a basic motif in the protein

Small molecule inhibitors of Aβ‐aggregation and neurotoxicity

Sugar microarray via click chemistry: molecular recognition with lectins and amyloid β (1–42)

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