Proteomic study of the toxic effect of oligomeric A beta 1-42 in situ prepared from 'iso-A beta 1-42'

Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders even so the exact pathomechanism is still unclear. Recently, it is widely accepted that amyloid-beta peptide (A beta ) toxicity is positively linked to A beta oligomers, which may be responsible for the initiation of AD. For this reason, AD research requires well defined aggregation state and structure of A beta . Precursor peptide 'iso-A beta 1-42' makes it possible to use A beta 1-42 with well- defined aggregation state for in vitro and in vivo experiments. The aim of this study was to identify protein expression changes from differentiated SH-SY5Y neuroblastoma cells after treatment with oligomeric A beta 1-42 prepared in situ from 'iso-A beta 1-42'. In our experiment, a cell viability assay revealed a strong and time-dependent toxic effect of oligomeric A beta 1-42 which was supported by dramatic morphological changes. Our proteomics study also revealed numerous significant protein expression changes (22 proteins down- and 25 proteins up-regulated) after comparison of the untreated and A beta 1-42-treated cell lysates by two-dimensional electrophoresis. From the functional classification of the identified proteins, we found deregulations of proteins involved in metabolic processes, cytoskeleton organisation and protein biosynthesis and a huge number of up-regulated stress proteins displayed oligomeric A beta 1-42-induced cell stress.Original Abstract: J. Neurochem. (2011) 117, 691-702.