Metachromatic leukodystrophy: consequences of sulphatide accumulation.
Metachromatic leukodystrophy is a lysosomal lipid storage disorder. It is caused by mutations in the gene for arylsulphatase A, an enzyme involved in the degradation of the sphingolipid 3'-O-sulphogalactosylceramide (sulphatide). This membrane lipid can be found in various cell types, but in particularly high concentrations in the myelin of the nervous system. Patients suffer from progressive, finally lethal, demyelination due to accumulation of sulphatide. In the nervous system, lipid storage not only affects oligodendrocytes but also neurons and, in addition, leads to astrogliosis and activation of microglia. At the cellular level, lysosomal sulphatide storage also affects the lipid composition of myelin itself and has consequences for the amount and localization of particular myelin membrane-associated proteins. Here we review data, largely based on an arylsulphatase A knock-out mouse model of metachromatic leukodystrophy.


CONCLUSIONS
The knock-out mouse model of metachromatic leukodystrophy has provided insights into the histopathological and cellular consequences of sulphatide storage.
Gieselmann
V
V
Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany. gieselmann@institut.physiochem.uni-bonn.de
Franken
S
S
Klein
D
D
Mansson
J E
JE
Sandhoff
R
R
Lüllmann Rauch
R
R
Hartmann
D
D
Saravanan
V P M
VP
De Deyn
P P
PP
D'Hooge
R
R
Van Der Linden
A M
AM
Schaeren-Wiemers
N
N
D000818:Animals; D001192:Arylsulfatases / Q000172:deficiency / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002553:Cerebroside-Sulfatase; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007966:Leukodystrophy, Metachromatic / Q000201:enzymology / Q000378:metabolism*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism
D008563:Membrane Lipids; D018992:Myelin-Associated Glycoprotein; D001192:Arylsulfatases; D002553:Cerebroside-Sulfatase