Deranged expression of molecular chaperones in brains of patients with Alzheimer's disease.
Alzheimer's disease (AD) is one of the disorders caused by protein conformational changes and recent studies have shown that several chaperone proteins are involved in this process. As information of chaperone expression in AD brain is limited, we aimed to study the expressional pattern of chaperones in several brain regions, as this may be essential to understand how folding defects can lead to disease. We studied the concomitant expressional patterns of molecular chaperones in seven brain regions of adults with AD using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-associated laser desorption ionization mass spectroscopy (MALDI-MS). We unambiguously identified and quantified nine different chaperone proteins. Six chaperone proteins, heat shock protein 60 (HSP 60), HSP 70 RY, heat shock cognate (HSC) 71, alpha crystallin B chain, glucose regulated protein (GRP) 75, and GRP 94 showed aberrant expressional patterns depending on brain region. HSP 70.1, GRP 78 and T-complex 1 (TCP-1) epsilon subunit did not show any significant expressional change. These findings are compatible with neuropathological and biochemical abnormalities in AD brain and this report presents the first approach to quantify nine different chaperones simultaneously at the protein level in individual AD brain regions providing evidence for the relevance of aberrant chaperone expression to AD neuropathology.
Yoo
B C
BC
Department of Pediatrics, University of Vienna, Vienna, Austria.
Kim
S H
SH
Cairns
N
N
Fountoulakis
M
M
Lubec
G
G
D000328:Adult; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001923:Brain Chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D006360:Heat-Shock Proteins; D018832:Molecular Chaperones