This article was originally published in the January 2019 edition of Matreya’s Newsletter for Glyco/Sphingolipid Research (PDF).

Sulfatides are 3’-sulfated galactosylceramides that are found primarily in the myelin sheath in the central nervous system. They are synthesized in the Golgi where ceramide that has been converted to galactocerebroside is sulfated to make sulfatide. To maintain appropriate levels, sulfatides are continuously degraded by lysosomes through the removal of their sulfate group via arylsulfatase A (ASA). Over the last several decades, sulfatides have been linked to many physiological functions and recently there has been a renewed interest in their role in diseases. Sulfatides are highly multifunctional glycolipids involved in diabetes, the immune system, hemostasis/thrombosis, bacterial infection, viral infection, and construction of the myelin sheath of the nervous system. By understanding the correlation between normal physiological functions of sulfatides and their specific roles in disease, new diagnostic and therapeutic methods can be evaluated.

Metachromatic leukodystrophy is caused by abnormal storage of sulfatides in the lysosomes of oligodendrocytes and to a lesser extent in astrocytes and some neurons due to a defect in their degradation by ASA.¹ The subsequent stress response results in an increased rate of oligodendrocyte apoptosis. Phagocytic clearance of the cell debris results in the progressive accumulation of undegradable sulfatides in microglial cells, eventually causing metabolic stress and microgliosis. Astrogliosis, elicited by sulfatide storage and/or microgliosis, might contribute to the progression of the neuroinflammatory process. Eventually, cytokines and other inflammatory factors secreted by the activated glial cells can become cytotoxic and induce widespread apoptosis of oligodendrocytes that are predisposed to damage by massive sulfatide storage. The loss of oligodendrocytes causes demyelination, which further magnifies neuroinflammation and causes neuronal dysfunction.

Metachromatic leukodystrophy is an autosomal-recessive lysosomal storage disease caused by mutations in the arylsulfatase A (ASA) gene, leading to ASA deficiency and causing sulfatide accumulation.

The main symptoms of metachromatic leukodystrophy are progressive demyelination, neurological dysfunction, and reduced life expectancy.² A comparative study analyzing sulfatide levels in newborn urine and dried blood spot samples concluded that urine, but not dried blood spots, was useful for screening newborns for metachromatic leukodystrophy.³

Sulfatides are highly dynamic glycosphingolipids with far-reaching biological processes. A greater understanding of these functions in living systems will lead to the elucidation of associated diseases and the development of therapeutic treatments for various sulfatide-associated diseases. Cayman offers deuterated, glycinated, sulfated, biotinylated, and fluorescent sulfatides in addition to the natural compounds that can be used to study their biological function.

Available Sulfatides

• Sulfatides (bovine) (sodium salt)


• 3’-sulfo Galactosylsphingosine (ammonium salt)


• N-Glycine 3’-sulfo Galactosylsphingosine


• C2 3'-sulfo Galactosylceramide (d18:1/2:0)


• C6 Biotin 3'-sulfo Galactosylceramide (d18:1/6:0)


• C12 3'-sulfo Galactosylceramide (d18:1/12:0)


• C16 3'-sulfo Galactosylceramide (d18:1/16:0)


• C17 3'-sulfo Galactosylceramide (d18:1/17:0)


• C18 3'-sulfo Galactosylceramide (d18:1/18:0)


• C18:1 3'-sulfo Galactosylceramide (d18:1/18:1(9Z))


• C19 3'-sulfo Galactosylceramide (d18:1/19:0)


• C24 3'-sulfo Galactosylceramide (d18:1/24:0)
  


• C24:1 3'-sulfo Galactosylceramide (d18:1/24:1(15Z))


• C12 NBD 3'-sulfo Galactosylceramide (d18:1/12:0)
  


• C18 3'-sulfo Lactosylceramide (d18:1/18:0)


• C18 3'-sulfo Galactosylceramide-d₃ (d18:1/18:0-d₃)

References

1. Zeng, Y., Cheng, H., Jiang, X., et al. Endosomes and lysosomes play distinct roles in sulfatide-induced neuroblastoma apoptosis: Potential mechanisms contributing to abnormal sulfatide metabolism in related neuronal diseases. Biochem. J. 410(1), 81-92 (2008).

2. Manshadi, M.D., Kamalidehghan, B., Aryani, O., et al. Four novel ARSA gene mutations with pathogenic impacts on metachromatic leukodystrophy: A bioinformatics approach to predict pathogenic mutations. Ther. Clin. Risk Manag. 13, 725-731 (2017).

3. Barcenas, M., Suhr, T.R., Scott, C.R., et al. Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry. Clin. Chim. Acta 433, 39-43 (2014).