Differential expression of molecular chaperones in brain of patients with Down syndrome

Heat shock proteins (HSPs) in their molecular capacity as chaperones have b een reported to regulate the apoptotic pathway and also play a critical rol e in protein conformational diseases such as Alzheimer's disease (AD). As a ll Down syndrome IDS) brains display AD-like neuropathology, neuronal loss in DS was shown to be mediated by apoptosis. We decided to investigate the expression patterns of HSPs in seven brain regions of adults with DS using two-dimensional polyacrylamide gel electrophoresis (2-DE). Following 2-DE, approximately 120 protein spots were successfully identified by matrix-assi sted laser desorption/ionization - mass spectrometry (MALDI-MS) followed by quantification of the identified proteins. We unambiguously identified and quantified nine different chaperone proteins. Accordingly, all but three c haperone proteins did exhibit a significant change in expression. HSP 70 RY , heat shock cognate (HSC) 71 and glucose-regulated protein (GRP) 75 showed a significant decrease (P< 0.05) in DS temporal cortex whereas HSP 70.1 an d GRP 78 were significantly increased (P<0.05) in cerebellum. Whilst T-comp lex 1 (TCP-I) epsilon subunit showed a significant decrease IP ( 0.05) in p arietal cortex, a similar extent of increase (P < 0.05) as that observed in cerebellum was obtained in parietal levels of GRP 78. Alpha-crystallin B, HSP 60 and GRP 94 did not show any detectable changes in expression pattern s. This report presents the first approach to quantify nine different chape rones simultaneously at the protein level in different brain regions and pr ovides evidence for aberrant chaperone expression patterns in DS. The relev ance of this aberrant expression patterns are discussed in relation to the biochemical and neuropathological abnormalities in DS brain.