Sulfatide

Aside from being a membrane component, sulfatide functions in protein trafficking, cell aggregation and adhesion, neural plasticity, memory, and glial-axon interactions.

Additionally, overexpression of sulfatide has been linked to epilepsy and audiogenic seizures as well as other pathological states in the nervous system.

It was named sulfatide in 1884 by Johann Ludwig Wilhelm Thudichum when he published "A Treatist of the Chemical Constitution of the Brain".

[1] This reaction occurs in the luminal leaflet of the endoplasmic reticulum, and its final product is GalCer, or galactocerebroside, which is then transported to the Golgi apparatus.

[1] Sulfatide has also been shown to play a role in myelin maintenance and glial-axon signaling, which was indicated by research in older cerebroside sulfotransferase (CST)-deficient mice.

[2][3] High levels of sulfatide in the gray matter in the cerebellum and in the superior frontal lobe have been associated with Parkinson's disease.

[2] Additionally, accumulation of sulfatide in neurons causes audiogenic seizures, which have been shown to be lethal in mouse models.

[2] On the other hand, reduced levels of sulfatide in the cerebral gray and white matter have been associated with Alzheimer's disease.

[2] Type 2 Natural killer T cells are able to recognize sulfatide/ CD1d tetramers, and as a result, they are activated by different tissues specific forms of sulfatide.

Type 2 Natural killer T cells that react with sulfatide help aid in protection from autoimmune disease and ischemic reperfusion.

[3] Additionally, when L-selectin and sulfatide bind, upregulation of the chemokine co-receptor's (CXCR4) expression is observed, specifically on the surfaced of leukocytes.

[3] Sulfatide may also function as a receptor for chemokines, which are small chemostatic cytokines, and they provide directional signals for leukocyte movement.

When an enhanced antibody response against myelin lipids occurs, including sulfatide in patients with multiple sclerosis, the demyelination process is increased significantly.

[7] When sulfatide and gangliosides are present, the proliferation or production of Natural Killer-T cells that produce cytokines are activated.

[3][5] Additionally, sulfatide is also found in the glandular stomach epithelium and in the apical membranes of the distal kidney tubuli where Myelin and lymphocyte protein (MAL) is expressed.

Myelin acts as an insulating sheath that surrounds many nerve fibers and increases the speed at which impulses are conducted.

When sulfatide is not distributed properly, it can affect the normal physiological conduction of electrical impulses between nerve cells.

[1] Sulfatide has several isoforms, including C16:0, which is found primarily in the secretory granules and toward the surface of the membrane of β cells.

When there are low serum levels of sulfatide, as well as elevated production of TNF-α in patients that have type II diabetes, it is commonly associated with insulin resistance.

[3] However, sulfatide may mediate suppression of type II diabetes through the activation of potassium protein channels.

[3] Specifically, cerebroside sulfotransferase (CST) is elevated as it passes along a signaling pathway which involves:[3] This path results in the accumulation of sulfatide in renal cancer cell lines.

This change in conformation allows the gp120 complex to interact with the chemokine co-receptor and the insertion of the fusion peptide, gp41, into the membrane of the host cell.

Guillain–Barré syndrome is classified as an acute autoimmune polyneuropathy, which specifically affects the peripheral nervous system of the infected patient.

[3] Several patients with Hepatitis C virus (HCV) associated with mixed cryoglobulinemia (MC) have elevated levels of anti-sulfatide antibodies in their blood plasma.

[2][3] Further experimentation has demonstrated that sulfatide enriched cells, in which sulfatide binds to hemagglutinin, enhances IAV replication by increasing the progeny virus particle formation; this is done through the promotion of nuclear export of IAV formed viral ribonucleoproteins from the nucleus to the cytoplasm.

Haemophilus influenzae, Bordetella pertussis, Mycoplasma pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa cause respiratory disease in humans.

[3] STb is an enterotoxin type B that is heat stable; additionally, it is secreted by the enterotoxigenic E. coli strain, and it causes diarrhoeal diseases in humans and many other species of animals.

The ε4 allele of apolipoprotein E is the only known genetic risk factor to significantly indicate late onset Alzheimer's disease.

[12][13] Vitamin K in the nervous system is responsible for the activation of enzymes that are essential for the biosynthesis of brain phospholipids, such as sulfatide.

[12] When warfarin, a vitamin K antagonist, is added to an animal model system, sulfatide synthesis is impaired.