Glycosaminoglycans from Alzheimer's disease hippocampus have altered capacities to bind and regulate growth factors activities and to bind tau

Minh Bao Huynh; Mohand Ouidir Ouidja; Sandrine Chantepie; Gilles Carpentier; Auriane Maïza; Ganlin Zhang; Joao Vilares; Rita Raisman-Vozari; Dulce Papy-Garcia

doi:10.1371/journal.pone.0209573

Glycosaminoglycans from Alzheimer's disease hippocampus have altered capacities to bind and regulate growth factors activities and to bind tau

PLoS One. 2019 Jan 4;14(1):e0209573. doi: 10.1371/journal.pone.0209573. eCollection 2019.

Authors

Minh Bao Huynh¹, Mohand Ouidir Ouidja¹, Sandrine Chantepie¹, Gilles Carpentier¹, Auriane Maïza¹, Ganlin Zhang¹, Joao Vilares², Rita Raisman-Vozari³, Dulce Papy-Garcia¹

Affiliations

¹ Cell Growth, Tissue Repair and Regeneration (CRRET), UPEC EA 4397/ERL CNRS 9215, Université Paris Est Créteil, Université Paris Est, Créteil, France.
² Aging and Neurodegenerative Diseases Brain Bank Investigation Laboratory, Universidade Federal de São Paulo, São Paulo, Brazil.
³ Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière (CRICM), Paris, France.

Abstract

Glycosaminoglycans (GAGs), including heparan sulfates and chondroitin sulfates, are major components of the extracellular matrix. Upon interacting with heparin binding growth factors (HBGF), GAGs participate to the maintaintenance of tissue homeostasis and contribute to self-healing. Although several processes regulated by HBGF are altered in Alzheimer's disease, it is unknown whether the brain GAG capacities to bind and regulate the function of HBGF or of other heparin binding proteins, as tau, are modified in this disease. Here, we show that total sulfated GAGs from hippocampus of Alzheimer's disease have altered capacities to bind and potentiate the activities of growth factors including FGF-2, VEGF, and BDNF while their capacity to bind to tau is remarkable increased. Alterations of GAG structures and capacities to interact with and regulate the activity of heparin binding proteins might contribute to impaired tissue homeostasis in the Alzheimer's disease brain.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / metabolism*
Brain / metabolism
Brain-Derived Neurotrophic Factor / metabolism
Brazil
Chondroitin Sulfates / metabolism
Extracellular Matrix / metabolism
Female
Fibroblast Growth Factor 2 / metabolism
Glycosaminoglycans / metabolism*
Heparin / metabolism
Heparitin Sulfate / metabolism
Hippocampus / metabolism
Humans
Male
Middle Aged
Protein Binding
Temporal Lobe / metabolism
Vascular Endothelial Growth Factor A / metabolism
tau Proteins / physiology*

Substances

Brain-Derived Neurotrophic Factor
Glycosaminoglycans
MAPT protein, human
VEGFA protein, human
Vascular Endothelial Growth Factor A
tau Proteins
Fibroblast Growth Factor 2
BDNF protein, human
Heparin
Chondroitin Sulfates
Heparitin Sulfate

Grants and funding

H2020 FET OPEN RIA ArrestAD project number 737390 supported research and gave salary for MBH. Fundation Vaincre Alzheimer grant number FR-15055 supported scholarship for AM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.