China
Africa
Explore chapters and articles related to this topic
Metachromatic leukodystrophy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The accumulated sulfatide leads to decreased content of cerebrosides and the other lipid components of myelin. Sulfatide is also found in increased quantity in the urine [108]. The amounts may be 100–200 times the normal level [109]. This property has sometimes been employed to identify patients for testing for saposin B deficiency in those with clinical MLD and normal ASA activity. Patients with pseudodeficiency do not have sulfatiduria [110].
Waldenström Macroglobulinemia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Although infrequent, organ damage may result from an IgM paraprotein with autoimmune activity or altered structure prone to tissue deposition [62]. Peripheral neuropathy, seen in approximately 25%–50% of patients [63], usually present as a distal, symmetric, and slowly progressive sensorimotor neuropathy with predominantly demyelinating features in nerve conduction studies [64]. Anti-myelin–associated glycoprotein (MAG) IgM antibodies have been implicated as the cause of neuropathy in half of these patients. IgM paraprotein directed to GD1b ganglioside, sulfatide, and chondroitin sulphate have also been described, although the causal relationship is not well established [64].
Diseases of the Nervous System
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
In metachromatic leukodystrophy or sulfatide lipidoses there is evidence of destruction of axons and the myelin sheaths with variable degrees and gliosis. Metachromatic deposits are present in affected areas usually as coarse homogenous globules in the brain, kidney, and bile ducts associated with dysfunction of these organs (Plate 6). There are two forms of this disease. The late infantile form begins between the ages of 3 and 5 months with death ensuing after about 10 months, preceded by weakness, ataxia, and hypotonus. The adult form shows initially psychological disturbances followed by progressive dementia. The biochemical lesion comprises the sulfatide, galactocerebroside-3-O-sulfate ester in both central and peripheral nerve tissues, resulting in a reduction in conduction of affected nerves. The defect is caused by a deficiency sulfuric acid esterase or sulfatase involved in sulfatidecatabolism. There are three distinct enzymes in normal tissue which differ in their subcellular localization, substrate affinity, and optimum pH. These are arylsulfatase A, B, and C. Arylsulfatase A is located predominantly in lysosomes. It is diminished in metachromatic leukodystrophy, and it is probable that ceramide-galactose-3-sulfate is the natural substrate of this enzyme. Other lysosomal enzymes show normal activity.
An appraisal of emerging therapeutic targets for multiple sclerosis derived from current preclinical models
Published in Expert Opinion on Therapeutic Targets, 2023
Aakanksha Dixit, Hannah S. Savage, Judith M. Greer
There are also many almost-untouched questions to be answered. When considering a disorder that specifically damages myelin, which consists of around 70–80% dry-weight of lipids, glycolipids (e.g., galactosylceramide and sulfatide) and glycosphingolipids (e.g. gangliosides), we need to consider how the presence of large amounts of these components in the local environment of the MS lesions affects the responses of other cells (as they can affect metabolism, damage neural networks, modulate immunity etc.) or impacts on therapeutic interventions. New unconventional T cell subsets that specifically interact with glycolipids have been identified, but as yet we don’t know if they can recognize these myelin-derived glycolipids in MS. Gangliosides have recently been identified as playing diverse roles in CNS development, particularly in axonogenesis (reviewed in [148]), but details are still to be elucidated.
Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells
Published in Gut Microbes, 2022
Yuyu Li, Yuchong Wang, Fan Shi, Xujun Zhang, Yongting Zhang, Kefan Bi, Xuequn Chen, Lanjuan Li, Hongyan Diao
Specifically, γδ T cells can be recognized and activated by lipid antigens presented by CD1d, a nonpolymorphic major histocompatibility class (MHC) I-like molecule.19 CD1d molecules are mainly expressed on the surface of antigen-presenting cells, hepatocytes and intestinal epithelial cells.20–23 Sulfatide, a lipid antigen, in the blood can be presented to a specific subset of γδ T cells through CD1d on the surface of antigen-presenting cells.24 Exogenous lipid antigens such as phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in the liver can also be presented to γδ T cells or natural killer T (NKT) cells through CD1d expressed by hepatocytes to promote activation.22,25–27 Moreover, γδ T cells in the mouse intestine can respond to lipid antigens presented by CD1d, including PE, PG and phosphatidylcholine (PC).23 Since the intestines constantly encounter lipid antigens derived from the commensal microbiota and acute hypoxia can significantly change the gut microbiota composition and structure, we speculate that lipid antigens derived from the intestinal microbiota may be related to the host immune response after acute hypoxia.
A review on neuropharmacological role of erucic acid: an omega-9 fatty acid from edible oils
Published in Nutritional Neuroscience, 2022
J. B. Senthil Kumar, Bhawna Sharma
Galactosylceramides (Figure 1(G)) and its sulphated version called sulfatide with long-chain fatty acid moieties, in particular 24:0 and 24:1 fatty acids, are considered to be the most typical myelin lipids [45]. The incorporation of these type of saturated and long-chain fatty acid are believed to influence the membrane thickness and the packing density of lipids within myelin. Mice that lack the enzyme UDP-galactose ceramide galactosyltransferase (CGT) (transfers galactose to ceramide in the biosynthesis of galactocerebroside) do not synthesise galactosylceramide and sulfatide and develop severe neurological deficits a few weeks after birth [41]. Similarly, a decrease in sulfogalactosyl ceramide (Figure 1(G)) has been reported in both grey matter and white matter of post mortem brains from AD subjects with mild dementia.