STUDIO DI ESPRESSIONE GENICA NELLA PATOLOGIA NEURODEGENERATIVA DI ALZHEIMER

Data inizio
1 gennaio 2010
Durata (mesi) 
12
Dipartimenti
Medicina
Responsabili (o referenti locali)
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.

Partecipanti al progetto

Luca Giuseppe Dalle Carbonare
Professore associato
Luca Donatelli
Maria Teresa Valenti
Tecnico-Amministrativo

Collaboratori esterni

Paolo Zatta
CNR Padova
Pubblicazioni
Titolo Autori Anno
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

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