Proteomic analysis of glial fibrillary acidic protein in Alzheimer's disease and aging brain.
Chronic inflammation is known to play an important role in the heterogeneous pathogenesis of Alzheimer's disease (AD). Activated astrocytes expressing glial fibrillary acidic protein (GFAP) are closely associated with AD pathology, such as tangles, neuritic plaques and amyloid depositions. Altogether, 46 soluble isoforms of GFAP were separated and most of them quantified by two-dimensional immunoblotting in frontal cortices of AD patients and age-matched controls. A 60% increase in the amount of more acidic isoforms of GFAP was observed in AD and these isoforms were both phosphorylated and N-glycosylated, while more basic isoforms were O-glycosylated and exhibited no quantitative differences between post-mortem AD and control brains. These data highlight the importance of exploring isoform-specific levels of proteins in pathophysiological conditions since modifications of proteins determine their activity state, localization, turnover and interaction with other molecules. Mechanisms, structures and functional consequences of modification of GFAP isoforms remain to be clarified.
Korolainen
Minna A
MA
Department of Neuroscience and Neurology, University of Kuopio, Harjulantie 1D, P.O. Box 1627, FIN-70211 Kuopio, Finland. Minna.Korolainen@uku.fi
Auriola
Seppo
S
Nyman
Tuula A
TA
Alafuzoff
Irina
I
Pirttilä
Tuula
T
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004660:Encephalitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005911:Gliosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D020033:Protein Isoforms / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics
D005904:Glial Fibrillary Acidic Protein; D020033:Protein Isoforms