MLD is a kind of lysosomal storage disorder due to the deficiency of the ARSA enzyme, which is involved in the metabolism of membrane sulfatides into galactosylceramide
. Progressive demyelination and dysfunction of the peripheral and central nervous systems is the symptom of this disease as the undegraded sulfatides require time to accumulate in oligodendrocytes and Schwann cells.
There are several ways to generate ceramide in mammalian cells (Figure 1): hydrolysis of sphingomyelin, de novo synthesis from palmitoyl-CoA and serine, catabolism of glucosylceramide and galactosylceramide
, synthesis from sphingosine and fatty acid, and dephosphorylation of ceramide-1-phosphate.
NNA - The American University of Beirut (AUB) has added another achievement to its formidable history in medical research, with the invention of Galactosylceramide
, the new drug to treat the CLN3 gene disease, one of the most dangerous diseases of children.
It is an autosomal recessive sphingolipidosis caused by deficient activity of the lysosomal enzyme galactosylceramide
beta-galactosidase (GALC) which degrades galactosylceramide
, a main component of myelin, and other terminal beta-galactose-containing sphingolipids, including psychosine (galactosylsphingosine). Increased psychosine levels lead to widespread destruction of oligodendroglia and impaired Schwann cell function in the central and peripheral nervous systems and to subsequent demyelination. It is so named due to the globoid cells (which are actually storage cells) infiltrating around cerebral blood vessels.
Furthermore, using thin-layer chromatography and mass spectrometry, it has been found that the insoluble aggregates of N-terminally truncated [PrP.sup.Sc] (i.e., PrP 27-30) contain small amounts of two host sphingolipids, galactosylceramide
and sphingomyelin , which also supports the localization of [PrP.sup.Sc] in rafts.
The virotoxin model of HIV-1 enteropathy: involvement of GPR15/Bob and galactosylceramide
in the cytopathic effects induced by HIV-1 gp120 in the HT-29-D4 intestinal cell line.
Piglet ileal mucus contains protein and glycolipid (Galactosylceramide
) receptors specific for Escherichia coli K88 Fimbriae.
Infection of colonic epithelial cell lines by Type I human immunodeficiency virus associated with cell surface expression of galactosylceramide
, a potential alternative gp120 receptor.
LC-MS/MS GALC assays were carried out with a close structural analog (galactosylceramide
, with a heptanoyl fatty acyl chain) of the natural substrate.
(2008) CLN3p impacts galactosylceramide
transport, raft morphology, and lipid content.
In lysosomal degradation, catabolism of GSLs occurs by cleavage of sugar residues which leads to the formation of glucosyl ceramide and galactosylceramide
. Thereafter, specific [beta]-glucosidases and galactosidases hydrolyze these lipids to produce ceramide that can later be deacylated by an acid ceramidase to form sphingosine [9, 16].
(2000) Biochemistry and neuropathology of mice doubly deficient in synthesis and degradation of galactosylceramide