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2 edition of Heparan sulfate regulates amyloid precursor processing by BACE1, the Alzeimer"s ß-secretase found in the catalog.

Heparan sulfate regulates amyloid precursor processing by BACE1, the Alzeimer"s ß-secretase

Zoe Michelle Scholefield

Heparan sulfate regulates amyloid precursor processing by BACE1, the Alzeimer"s ß-secretase

by Zoe Michelle Scholefield

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  • 39 Currently reading

Published by University of Birmingham in Birmingham .
Written in English


Edition Notes

Thesis (Ph.D.) - University of Birmingham, School of Biosciences.

Statementby Zoe Michelle Scholefield.
The Physical Object
Pagination295 p. ;
Number of Pages295
ID Numbers
Open LibraryOL21688710M

Scale bar, 1 mm. The percentage of area covered by plaques was quantified, and the plaque load was normalized to that of APP/PS1 mice. From Liu CC, Zhao N, Yamaguchi Y, et al. Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-β clearance and aggregation in Alzheimer's disease. Sci Translational Med. ;8( Hjertström, E. Roles of Heparan Sulfate in Amyloid-β Pathology and Hypoxia. Acta Universitatis Upsaliensis. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 55 pp. Uppsala. ISBN Heparan sulfate (HS) is a highly sulfated polysaccharide expressed on the cell surface and in.

Scholefield Z, Yates EA, Wayne G, Amour A, McDowell W, Turnbull JE () Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer’s beta-secretase. J Cell Biol , 97– [20].   Heparan sulfate proteoglycans (HSPGs) play an important role in these interactions, because they are components of both basement and plasma membranes (Iozzo et al., ; Bernfield et al., ). The anionic heparan sulfate (HS) glycosaminoglycan chains bind to extracellular matrix and cell surface proteins, providing a framework for matrix.

The acronym HS-GAG is used to describe both heparin and heparan sulfate. HS-GAG is a member of the glycosaminoglycan family and consists of a variably sulfated repeating disaccharide unit, the most common one (50% of the total) being glucuronic acid (GlcA) linked to N-acetylglucosamine (GlcNAc).   Heparan sulfate (HS) is a highly acidic linear polysaccharide with a very variable structure. It is ubiquitously expressed on cell surfaces and in the extracellular matrix and basement membrane of mammalian tissues. Synthesized attached to various core proteins to form HS-proteoglycans, HS is capable of interacting with various polypeptides and exerting diverse functions.


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Heparan sulfate regulates amyloid precursor processing by BACE1, the Alzeimer"s ß-secretase by Zoe Michelle Scholefield Download PDF EPUB FB2

Cleavage of amyloid precursor protein (APP) by the Alzheimer's β-secretase (BACE1) is a key step in generating amyloid β-peptide, the main component of amyloid plaques. Here we report evidence that heparan sulfate (HS) interacts with β-site APP-cleaving enzyme (BACE) 1 and regulates its cleavage of by: Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's beta-secretase Article (PDF Available) in The Journal of Cell Biology (1) November with.

DOI: /jcb Corpus ID: Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase @article{ScholefieldHeparanSR, title={Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase}, author={Zoe Scholefield and Edwin A.

Yates and Gareth J Wayne and Augustin Amour. DOI: /jcb Corpus ID: Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase @article{ScholefieldHeparanSR, title={Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase}, author={Zoe Scholefield and Edwin A Yates and Gareth J Wayne and Augustin Amour.

the Alzeimers ß-secretase book Furthermore, Alzheimer β-secretase (BACE1: β-site amyloid precursor protein-cleaving enzyme 1) is an aspartic protease that generates the amino terminus of β-amyloid protein from the APP.

BACE1 is a key target for Alzheimer drug development, because it is implicated in the rate-limiting step in the formation of by:   Aβ is generated from proteolytic processing of amyloid precursor protein (APP) by β- and γ-secretases (3, 4).

Genetic and biochemical studies showed that early-onset forms of AD (processing, leading to increases in Aβ production or the propensity for Aβ to. Patey SJ, Edwards EA, Yates EA, Turnbull JE. Med. Chem. Oct;49(20) PMID: Abstract. Heparan sulfate (HS) regulates processing of the amyloid precursor protein by the Alzheimer’s beta-secretase (BACE-1).

Kalimo H, Lindahl U, Lannfelt L, Zhang X. () Heparan sulfate accumulation with amyloid- deposits in Alzheimer's disease and Tg mice is contributed by glial cells.

Brain Pathology, II O’Callaghan P, Li JP, Lindahl U, Lannfelt L, Zhang X. () Microglial heparan sulfate proteoglycans mediate pro-inflammatory signaling. Heparan sulfate (HS) and HS proteoglycans (HSPGs) colocalize with Aβ in brains of AD patients and transgenic animals overexpressing mutant human amyloid-beta precursor protein (AβPP) (O'Callaghan et al.

; Snow et al; Snow et al. ; van Horssen et al. ; van Horssen et al. HSPGs are ubiquitous on cell surfaces and in the. Scholefield Z, Yates EA, Wayne G, Amour A, McDowell W, Turnbull JE. Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase.

Journal of Cell Biology. ; (1)– [PMC free article]. Z. Scholefield, E.A. Yates, G. Wayne, et n sulfate regulates amyloid precursor protein processing by BACE, the Alzheimer’s β. Scholefield Z, Yates EA, Wayne G, Amour A, McDowell W, et al.

Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's beta-secretase. J Cell Biol 97– PubMed Google Scholar.

B. Regulatory Roles of HS in Processing of Amyloid Precursor Proteins. Most of the amyloid peptides are derived from their precursors; an example is Aβ, a proteolytic product of AβPP. AβPP is a type I transmembrane protein with one form of aa predominantly expressed in neurons, and the forms of and aa expressed in other cells.

Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (HSPG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins. It is in this form that HS binds to a variety of protein ligands, including Wnt, and regulates a wide range of biological activities, including developmental processes.

Processing of amyloid beta precursor protein (APP) into amyloid-beta peptide (Aβ) by β-secretase and γ-secretase complex is at the heart of the pathogenesis of Alzheimer’s disease (AD). Hajime Shimizu, Mohammad Ghazizadeh, Shigeru Sato, Tatsuo Oguro, Oichi Kawanami, Interaction between β-amyloid protein and heparan sulfate proteoglycans from the cerebral capillary basement membrane in Alzheimer’s disease, Journal of Clinical Neuroscience, /, 16, 2, (), ().

In vivo fragmentation of heparan sulfate by heparanase overexpression renders mice resistant to amyloid protein A amyloidosis. Proc Natl Acad Sci. The pathological Aβ peptides composed of 40 or 42 amino acids are products of sequential cleavage of the amyloid β precursor protein (APP) by β-secretase (β-site APP cleaving enzyme 1: BACE1, a membrane-bound aspartyl protease) (Cai et al., ) and γ-secretase (Bergmans & Strooper, ).

Sandra G. Velleman, Caini Liu, in Chemistry and Biology of Heparin and Heparan Sulfate, XII Summary. The heparan sulfate proteoglycans represent a large family of both cell surface and pericellular macromolecules. Although not completely understood at this time, it is clear that subtle changes in heparan sulfate structure and macromolecular organization of the core protein can.

The Heparin/Heparan Sulfate-binding Site on Apo-serum Amyloid A ApoSAA is also the precursor of inflammation-associated amyloid, and there is strong evidence that the formation of inflammation-associated and other types of amyloid is promoted by heparan sulfate (HS).

Data presented herein demonstrate that both mouse and human apoSAA contain. Besides amyloid, heparan sulfate proteoglycan (HSPG), is commonly found in most amyloid deposits, suggesting that HS/HSPG may be functionally involved in the pathogenesis of amyloidosis. HS or HSPG is found to interact with a number of amyloid proteins, displaying a promoting effect on amyloid fibrilization in vitro.Heparan sulfate 6-O-sulfotransferases (HS6STs), which catalyze the transfer of sulfate from 3′-phospho adenosine 5′-phosphosulfate (PAPS) to position 6 of N-sulfoglucosamine and N-acetylglucosamine residues in HS, are derived from three different genes, Hs6st-1, -2, and -3 and one alternatively spliced form of Hs6st-2 (Hs6st-2S).

17–  Clasper, S. et al. Inducible expression of the cell surface heparan sulfate proteoglycan syndecan-2 (fibroglycan) on human activated macrophages can regulate fibroblast growth factor action.

J. .