Heparan Sulfate Subdomains that are Degraded by Sulf Accumulate in Cerebral Amyloid ß Plaques of Alzheimer's Disease

Hosono-Fukao, Tomomi; Ohtake-Niimi, Shiori; Hoshino, Hiroo; Britschgi, Markus; Akatsu, Hiroyasu; Hossain, Md. Motarab; Nishitsuji, Kazuchika; Kuppevelt, Toin H. Van; Kimata, Koji; Michikawa, Makoto; Wyss‐Coray, Tony; Uchimura, Kenji

doi:10.1016/j.ajpath.2012.01.015

Cited by 41 publications

(30 citation statements)

References 59 publications

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“…Lung and eosinophil keratan sulfate was isolated and analyzed as described previously for heparan sulfate (51) with slight modifications. Lung left lobes were dissected out from three adult mice (∼150 mg), and peripheral blood leukocytes (60 × 10 6 ) were obtained from the blood of IL-5 transgenic mice.…”

Section: Methodsmentioning

confidence: 99%

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Patnode

Cheng

Chou

et al. 2013

Journal of Biological Chemistry

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Background: The cell surface lectin Siglec-F is thought to preferentially recognize ligands modified with galactose 6-O-sulfate.Results: Siglec-F ligands are still present in leukocytes and lung tissue from mice lacking galactose 6-O-sulfotransferases.Conclusion: Ligands are restricted to specific cell types, but galactose 6-O-sulfotransferases are not required for ligand binding.Significance: This study refines our understanding of the biological ligands for Siglec-F.

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Section: Methodsmentioning

confidence: 99%

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Patnode

Cheng

Chou

et al. 2013

Journal of Biological Chemistry

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“…Sulf-1 and Sulf-2 reportedly regulated several signaling pathways that were governed by molecular interactions between HS and protein ligands in extracellular spaces (16). We previously showed that highly sulfated domains of HS accumulated in amyloid plaques in patients with AD (26). Presumably, these highly sulfated domains could contribute to the pathology of amyloidosis.…”

Section: Discussionmentioning

confidence: 99%

“…HS was also associated with various types of amyloid in disorders other than AA amyloidosis, including the amyloid in amyloid light chain amyloidosis (22), amyloid-␤ (A␤) of Alzheimer disease (AD) (23)(24)(25)(26), prion protein in Creutzfeldt-Jakob disease (27), and islet amyloid polypeptide in the islets of Langerhans of type 2 diabetes (28). We and others showed that HS mediated the cellular uptake of A␤ and the cellular association with A␤ (29,30).…”

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confidence: 99%

Cellular Interaction and Cytotoxicity of the Iowa Mutation of Apolipoprotein A-I (ApoA-IIowa) Amyloid Mediated by Sulfate Moieties of Heparan Sulfate

Kuwabara

Nishitsuji

Uchimura

et al. 2015

Journal of Biological Chemistry

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Background:The G26R apolipoprotein A-I (apoA-I Iowa ) mutation causes familial amyloid polyneuropathy. Results: ApoA-I Iowa amyloid cellular interaction and cytotoxicity depended on cell surface heparan sulfate (HS). Enzymatic remodeling of HS by extracellular sulfatase mitigated cytotoxicity. Conclusion: Sulfate moieties of cell surface HS are critical for mediating apoA-I amyloid cytotoxicity. Significance: Enzymatic remodeling of HS may be a novel concept for regulating actions of amyloid on cells.

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“…This antibody strongly stained both diffuse and neuritic A β plaques in the brains of AD and several transgenic AD mouse models. Interestingly, the RB4CD12 epitope accumulated in A β plaques can be demolished by extracellular sulfatases (Sulf-1 and Sulf-2) ex vivo [72], suggesting that 6-O-sulfated glucosamine residues are within the HS sequence interacting with A β .…”

Section: Codeposition Of Hs With Aβ In Ad Brain—updated Findingsmentioning

confidence: 99%

Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer’s Disease

Zhang

Wang

et al. 2014

BioMed Research International

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Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive loss of memory and cognitive dysfunctions. A central pathological event of AD is accumulation and deposition of cytotoxic amyloid-β peptide (Aβ) in the brain parenchyma. Heparan sulfate proteoglycans (HSPGs) and the side chains heparan sulfate (HS) are found associated with Aβ deposits in the brains of AD patients and transgenic animal models of AD. A growing body of evidence from in vitro and in vivo studies suggests functional roles of HSPG/HS in Aβ pathogenesis. Although the question of “how and why HSPG/HS is codeposited with Aβ?” still remains, it is within reach to understand the mechanisms of the events. Recent progress by immunohistochemical examination with advanced antibodies shed light on molecular structures of HS codeposited with Aβ. Several recent reports have provided important new insights into the roles of HSPG in Aβ pathogenesis. Particularly, experiments on mouse models revealed indispensible functions of HSPG in modulating Aβ-associated neuroinflammation and clearance of Aβ from the brain. Application of molecules to interfere with the interaction between HS and Aβ peptides has demonstrated beneficial effects on AD mouse models. Elucidating the functions of HSPG/HS in Aβ deposition and toxicity is leading to further understanding of the complex pathology of AD. The progress is encouraging development of new treatments for AD by targeting HS-Aβ interactions.

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Heparan Sulfate Subdomains that are Degraded by Sulf Accumulate in Cerebral Amyloid ß Plaques of Alzheimer's Disease

Cited by 41 publications

References 59 publications

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Galactose 6-O-Sulfotransferases Are Not Required for the Generation of Siglec-F Ligands in Leukocytes or Lung Tissue

Cellular Interaction and Cytotoxicity of the Iowa Mutation of Apolipoprotein A-I (ApoA-IIowa) Amyloid Mediated by Sulfate Moieties of Heparan Sulfate

Towards Understanding the Roles of Heparan Sulfate Proteoglycans in Alzheimer’s Disease

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