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Increased 3-O-sulfated heparan sulfate in Alzheimer's disease brain is associated with genetic risk gene HS3ST1.
Wang, Zhangjie; Patel, Vaishali N; Song, Xuehong; Xu, Yongmei; Kaminski, Andrea M; Doan, Vivien Uyen; Su, Guowei; Liao, Yien; Mah, Dylan; Zhang, Fuming; Pagadala, Vijayakanth; Wang, Chunyu; Pedersen, Lars C; Wang, Lianchun; Hoffman, Matthew P; Gearing, Marla; Liu, Jian.
Afiliación
  • Wang Z; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Patel VN; Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD 20892, USA.
  • Song X; Department of Molecular Pharmacology and Physiology, Byrd Alzheimer's Center and Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612 USA.
  • Xu Y; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Kaminski AM; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
  • Doan VU; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Su G; Glycan Therapeutics Corp., 617 Hutton Street, Raleigh, NC 27606, USA.
  • Liao Y; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Mah D; Department of Biological Sciences, Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Zhang F; Department of Biological Sciences, Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Pagadala V; Glycan Therapeutics Corp., 617 Hutton Street, Raleigh, NC 27606, USA.
  • Wang C; Department of Biological Sciences, Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA.
  • Pedersen LC; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
  • Wang L; Department of Molecular Pharmacology and Physiology, Byrd Alzheimer's Center and Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612 USA.
  • Hoffman MP; Matrix and Morphogenesis Section, National Institute of Dental and Craniofacial Research, NIH, DHHS, Bethesda, MD 20892, USA.
  • Gearing M; Department of Pathology and Laboratory Medicine and Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Liu J; Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Sci Adv ; 9(21): eadf6232, 2023 05 26.
Article en En | MEDLINE | ID: mdl-37235665
HS3ST1 is a genetic risk gene associated with Alzheimer's disease (AD) and overexpressed in patients, but how it contributes to the disease progression is unknown. We report the analysis of brain heparan sulfate (HS) from AD and other tauopathies using a LC-MS/MS method. A specific 3-O-sulfated HS displayed sevenfold increase in the AD group (n = 14, P < 0.0005). Analysis of the HS modified by recombinant sulfotransferases and HS from genetic knockout mice revealed that the specific 3-O-sulfated HS is made by 3-O-sulfotransferase isoform 1 (3-OST-1), which is encoded by the HS3ST1 gene. A synthetic tetradecasaccharide (14-mer) carrying the specific 3-O-sulfated domain displayed stronger inhibition for tau internalization than a 14-mer without the domain, suggesting that the 3-O-sulfated HS is used in tau cellular uptake. Our findings suggest that the overexpression of HS3ST1 gene may enhance the spread of tau pathology, uncovering a previously unidentified therapeutic target for AD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Alzheimer Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos