Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Brain Pathology in Mucopolysaccharidoses (MPS) Patients with Neurological Forms

Full text
Author(s):
Viana, Gustavo M. [1, 2] ; Priestman, David A. [3] ; Platt, Frances M. [3] ; Khan, Shaukat [4] ; Tomatsu, Shunji [4] ; Pshezhetsky, Alexey V. [3, 1, 2]
Total Authors: 6
Affiliation:
[1] CHU Ste Justine, Res Ctr, Div Med Genet, Montreal, PQ H3T 1C5 - Canada
[2] Fed Univ Sao Paulo UNIFESP, Dept Biochem, BR-04044020 Sao Paulo, SP - Brazil
[3] Univ Oxford, Dept Pharmacol, Oxford OX1 3SZ - England
[4] Nemours Alfred I duPont Hosp Children, Wilmington, DE 19801 - USA
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF CLINICAL MEDICINE; v. 9, n. 2 FEB 2020.
Web of Science Citations: 0
Abstract

Mucopolysaccharidoses (MPS) are the group of lysosomal storage disorders caused by deficiencies of enzymes involved in the stepwise degradation of glycosaminoglycans. To identify brain pathology common for neurological MPS, we conducted a comprehensive analysis of brain cortex tissues from post-mortem autopsy materials of eight patients affected with MPS I, II, IIIA, IIIC, and IIID, and age-matched controls. Frozen brain tissues were analyzed for the abundance of glycosaminoglycans (heparan, dermatan, and keratan sulfates) by LC-MS/MS, glycosphingolipids by normal phase HPLC, and presence of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor superfamily member 10 (TNFSF10) by Western blotting. Fixed tissues were stained for the markers for microgliosis, astrogliosis, misfolded proteins, impaired autophagy, and GM2 ganglioside. Our results demonstrate that increase of heparan sulfate, decrease of keratan sulfate, and storage of simple monosialogangliosides 2 and 3 (GM2 and GM3) as well as the neutral glycosphingolipid, LacCer, together with neuroinflammation and neuronal accumulation of misfolded proteins are the hallmarks of brain pathology in MPS patients. These biomarkers are similar to those reported in the corresponding mouse models, suggesting that the pathological mechanism is common for all neurological MPS in humans and mice. (AU)

FAPESP's process: 18/17003-6 - Glycosaminoglycans as triggers of neurodegeneration in MPS IIIC and Alzheimer's Disease
Grantee:Gustavo Monteiro Viana
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor