Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain.
Protein glycosylation modifies the processing of several key proteins involved in the molecular pathogenesis of Alzheimer's disease (AD). Aberrant glycosylation of tau and down-regulation of sialyltransferase in AD brain suggest a possible dysregulation of protein glycosylation that may play a role in AD. We therefore isolated major glycoproteins from AD brain by using lectin-affinity chromatographies and ion-exchange chromatography and further separated them using SDS-polyacylamide gel electrophoresis. Mass spectrometry analysis of 11 isolated glycoproteins led to their identification as: neuronal cell adhesion molecule, beta-globin, IgM heavy chain VH1 region precursor, contactin precursor, dipeptidylpeptidase VI, CD81 partner 3, prenylcysteine lyase, adipocyte plasma-associated protein, acid ceramidase and two novel proteins. We found that the level and activity of acid ceramidase (AC), one of the major identified human brain glycoproteins, were significantly elevated in AD brain. Immunohistochemical staining indicated that AC was located mainly in the cell bodies of neurons and colocalized with neurofibrillary tangles. Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC-mediated signalling pathways might be involved in the molecular mechanism of AD.
Huang
Yu
Y
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314-6399, USA.
Tanimukai
Hitoshi
H
Liu
Fei
F
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
Gong
Cheng-Xin
CX
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation / Q000502:physiology; D002517:Galactosylgalactosylglucosylceramidase / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008875:Middle Aged
D002517:Galactosylgalactosylglucosylceramidase