STUDIO DI ESPRESSIONE GENICA NELLA PATOLOGIA NEURODEGENERATIVA DI ALZHEIMER

Starting date
January 1, 2010
Duration (months)
12
Departments
Medicine
Managers or local contacts
Dalle Carbonare Luca Giuseppe

A typical pathological feature of Alzheimer's disease (AD) is the appearance in the brain of senile plaques made up of β-amyloid (Aβ) 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 Aβ aggregation and neurotoxicity.
In this study, employing a microarray analysis of 35,129 genes, we investigated the effects induced by the exposure to the Aβ(1-42)-Al (Aβ-Al) complex on the gene expression profile of the neuronal-like cell line, SH-SY5Y.
The microarray assay indicated that, compared to Aβ or Al alone, exposure to Aβ-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.
Aβ-Al appears to be largely involved in the molecular machinery that regulates neuronal as well as synaptic dysfunction and loss. Aβ-Al seems critical in modulating key AD-related pathways such as glutamatergic transmission, Ca(2+) homeostasis, oxidative stress, inflammation, and neuronal apoptosis.

Project participants

Luca Giuseppe Dalle Carbonare
Associate Professor
Luca Donatelli
Maria Teresa Valenti
Temporary Professor

Collaboratori esterni

Paolo Zatta
CNR Padova
Publications
Title Authors Year
Microarray analysis on human neuroblastoma cells exposed to aluminum, ²(1-42)-amyloid or the ²(1-42)-amyloid aluminum complex. Gatta V; Drago D; Fincati K; Valenti MT; Dalle Carbonare L; Sensi SL; Zatta P. 2011

Activities

Research facilities