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

Minh Bao Huynh (1) , Mohand Ouidir Ouidja (1) , Sandrine Chantepie (1) , Gilles Carpentier (1) , Auriane Maïza (1) , Ganlin Zhang (1) , Joao Vilares (2) , Rita Raisman-Vozari (3) , Dulce Papy-Garcia (1)

1 CRRET - Croissance cellulaire, réparation et régénération tissulaires
2 Unifesp - Federal University of Sao Paulo
3 ICM - Institut du Cerveau = Paris Brain Institute

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.

Mots clés: Alzheimer's disease; Heparin; Sulfation; Cell binding assay; Homeostasis; Hippocampus; Growth factors; Enzyme-linked immunoassays

Domaines: Neurobiologie

Minh Bao Huynh, Mohand Ouidir Ouidja, Sandrine Chantepie, Gilles Carpentier, Auriane Maïza, et al.. Glycosaminoglycans from Alzheimer’s disease hippocampus have altered capacities to bind and regulate growth factors activities and to bind tau. PLoS ONE, 2019, 14 (1), pp.e0209573. ⟨10.1371/journal.pone.0209573⟩. ⟨hal-01983707⟩