Glycosylation changes in Alzheimer's disease as revealed by a proteomic approach.
Glycosylation influences the biological activity of proteins and affects their folding and stability. Because aberrant glycosylation is associated with Alzheimer's disease (AD), we applied proteome analysis together with Pro-Q Emerald 300 glycoprotein staining to investigate changes in glycosylated cytosolic proteins in AD and control brain. Frontal cortex proteins from 10 AD patients and 7 non-demented controls were subjected to separation by two-dimensional gel electrophoresis and subsequently stained with carbohydrate-specific Pro-Q Emerald 300 dye. Changes in glycosylation of separated proteins were quantified, and proteins of interest identified by mass spectrometry. Approximately 30% of all detectable proteins in the human frontal cortex appeared glycosylated, including heat shock cognate 71 stress protein and beta isoform of creatine kinase. The glycosylation of collapsin response mediator protein 2 (CRMP-2) and an unknown protein was reduced in AD, while the glycosylation of glial fibrillary acidic protein was increased. CRMP-2 regulates the assembly and polymerization of microtubules and is associated with neurofibrillary tangles in AD. Aberrant glycosylations in AD may help understand the mechanisms of neurodegenerative diseases.
Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, Neulaniementie 2, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Katja
K
Kanninen
Gundars
G
Goldsteins
Seppo
S
Auriola
Irina
I
Alafuzoff
Jari
J
Koistinaho
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry; D004396:Coloring Agents; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2