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Mol Neurobiol (2008) 37:93103 DOI 10.1007/s12035-008-8022-3
The Role and Metabolism of Sulfatide in the Nervous System
Matthias Eckhardt
Received: 25 February 2008 /Accepted: 9 April 2008 /Published online: 9 May 2008 # Humana Press Inc. 2008
Abstract 3-O-sulfogalactosylceramide or sulfatide is a major component of the myelin sheath in the central and peripheral nervous system. The examination of mice deficient in the sulfatide-synthesizing enzyme, cerebroside sulfotransferase, provided new insight into the role of sulfatide in the differentiation of myelinating cells, formation of the paranodal junction, and myelin maintenance. Although in general regarded as a marker for oligodendrocytes and Schwann cells, sulfatide is also present in astrocytes and neurons. The relatively low amount of sulfatide in neurons can dramatically increase in the absence of the sulfatide-degrading enzyme, arylsulfatase A, as in metachromatic leukodystrophy. Recent advance in the understanding of this disease comes from studies on new transgenic mouse models. Significant changes in sulfatide levels have also been observed more recently in Alzheimers disease and other diseases, suggesting that sulfatide might be involved in the pathogenesis of these diseases as well. This review summarizes recent studies on the physiological and pathophysiological role of sulfatide using transgenic mice deficient in its synthesis or degradation.
Keywords Alzheimers disease . Galactosylceramide .
Metachromatic leukodystrophy. Myelin . Oligodendrocytes . Schwann cells . Sphingolipids . Sulfatide
Introduction
Glycosphingolipids are abundant components of cellular membranes in all eukaryotic cells. They play important roles in various physiological and pathophysiological processes (for a review, see [13]). A major fraction of glycolipids in the mammalian nervous system is build up by sulfoglycolipids. The first sulfoglycolipid in mammals was described by Thudichum in 1884 [4] who isolated the most abundant brain sulfoglycolipid, 3-O-sulfogalactosylceramide (sulfatide; SM4s; SGalCer), from human brain. Other sulfoglycolipids found in the mammalian brain are 3-O-sulfogalactosylglycerolipids (sulfogalactosyldiacylglycerol and the etherlipid/plasmalogen sulfogalactosylalkylacylglycerol or seminolipid, which is found at high concentration in the testis), and glycolipids carrying sulfated glucuronyl lactosaminyl residues [5, 6]. Mice deficient in this structure (HNK-1 epitope) have been generated, showing alterations in synaptic efficacy, learning, and memory [7, 8]. Because the HNK-1 structure is also a posttranslational modification of various adhesion molecules and other proteins, it is difficult to examine a specific role for lipid-linked HNK-1 structure using these mice. Other sulfolipids, like...