FN Archimer Export Format
PT J
TI Low-molecular weight sulfated marine polysaccharides: Promising molecules to prevent neurodegeneration in mucopolysaccharidosis IIIA?
BT 
AF Veraldi, Noemi
   Quadri, Isabelle Dentand
   van de Looij, Yohan
   Modernell, Laura Malaguti
   Sinquin, Corinne
   Zykwinska, Agata
   Tournier, Benjamin B.
   Dalonneau, Fabien
   Li, Honglian
   Li, Jin-Ping
   Millet, Philippe
   Vives, Romain
   COLLIEC JOUAULT, Sylvia
   de Agostini, Ariane
   Farias Sanches, Eduardo
   Sizonenko, Stéphane V.
AS 1:1;2:2;3:3,4;4:4;5:5;6:5;7:6;8:7;9:8;10:8;11:6;12:7;13:5;14:1,2;15:4;16:4;
FF 1:;2:;3:;4:;5:PDG-RBE-MASAE-LEMMMB;6:PDG-RBE-MASAE-LEMMMB;7:;8:;9:;10:;11:;12:;13:PDG-RBE-MASAE-LEMMMB;14:;15:;16:;
C1 Division of Clinical Pathology, Department of Diagnostics, Geneva University Hospitals, Geneva, Switzerland
   Department of Pathology and Immunology, Faculty of Medicine, Geneva University, Geneva, Switzerland
   Center for Biomedical Imaging, Animal Imaging Technology section, Federal Polytechnic School of Lausanne, Lausanne, Switzerland
   Division of Development and Growth, Department of Pediatrics & Gynecology & Obstetrics, Children's Hospital, Geneva University Hospitals, Geneva, Switzerland
   Ifremer, Atlantic Center, MASAE, Nantes, France
   Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland
   University of Grenoble Alpes, CNRS, CEA, IBS, Grenoble, France
   Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden
C2 UNIV GENEVA, SWITZERLAND
   UNIV GENEVA, SWITZERLAND
   EPFL, SWITZERLAND
   DIVISION OF DEVELOPMENT AND GROWTH, SWITZERLAND
   IFREMER, FRANCE
   UNIV GENEVA, SWITZERLAND
   UNIV GRENOBLE ALPES, FRANCE
   UNIV UPPSALA, SWEDEN
SI NANTES
SE PDG-RBE-MASAE-LEMMMB
IN WOS Ifremer UPR
   copubli-france
   copubli-europe
   copubli-univ-france
   copubli-int-hors-europe
IF 11.2
TC 1
UR https://archimer.ifremer.fr/doc/00847/95880/103765.pdf
   https://archimer.ifremer.fr/doc/00847/95880/103766.pdf
LA English
DT Article
DE ;Heparan sulfate;Mucopolysaccharidosis;Marine polysaccharides;Magnetic spectroscopy resonance
AB Mucopolysaccharidosis IIIA is a hereditary disease caused by mutations in the sulfamidase enzyme that participates in catabolism of heparan sulfate (HS), leading to HS fragment accumulation and multisystemic failure. No cure exists and death occurs around the second decade of life. Two low molecular weight highly sulfated compounds derived from marine diabolican and infernan exopolysaccharides (A5_3 and A5_4, respectively) with heparanase inhibiting properties were tested in a MPSIIIA cell line model, resulting in limited degradation of intracellular HS. Next, we observed the effects of intraperitoneal injections of the diabolican derivative A5_3 from 4 to 12 weeks of age on MPSIIIA mice. Brain metabolism and microstructure, levels of proteins and genes involved in MPSIIIA brain pathophysiology were also investigated. 1H-Magnetic Resonance Spectroscopy (MRS) indicated deficits in energetic metabolism, tissue integrity and neurotransmission at both 4 and 12 weeks in MPSIIIA mice, with partial protective effects of A5_3. Ex-vivo Diffusion Tensor Imaging (DTI) showed white matter microstructural damage in MPSIIIA, with noticeable protective effects of A5_3. Protein and gene expression assessments displayed both pro-inflammatory and pro-apoptotic profiles in MPSIIIA mice, with benefits of A5_3 counteracting neuroinflammation. Overall, derivative A5_3 was well tolerated and was shown to be efficient in preventing brain metabolism failure and inflammation, resulting in preserved brain microstructure in the context of MPSIIIA. 
PY 2023
PD NOV
SO Carbohydrate Polymers
SN 0144-8617
PU Elsevier BV
VL 320
UT 001047329400001
DI 10.1016/j.carbpol.2023.121214
ID 95880
ER

EF