Microarray analysis on human neuroblastoma cells exposed to aluminum, ?(1-42)-amyloid or the ?(1-42)-amyloid aluminum complex.

ABSTRACT: BACKGROUND: A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of ?-amyloid (A?) and neurofibrillary tangles. AD is also associated with an abnormal accumulation of some metal ions, and we have recently shown that one of these, aluminum (Al), plays a relevant role in affecting A? aggregation and neurotoxicity. METHODOLOGY: In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the A?(1-42)-Al (A?-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y. PRINCIPAL FINDINGS: The microarray assay indicated that, compared to A? or Al alone, exposure to A?-Al complex produced selective changes in gene expression. Some of the genes selectively over or underexpressed are directly related to AD. A further evaluation performed with Ingenuity Pathway analysis revealed that these genes are nodes of networks and pathways that are involved in the modulation of Ca(2+) homeostasis as well as in the regulation of glutamatergic transmission and synaptic plasticity. CONCLUSIONS AND SIGNIFICANCE: A?-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. A?-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca(2+) homeostasis, oxidative stress, inflammation, and neuronal apoptosis.

SUBMITTER: Gatta V 

PROVIDER: S-EPMC3029275 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature