ABSTRACT
Title
Understanding β-Amyloid-induced toxicity by a chemical-biology approach.
Authors
M. Camarri1, L. Terzuoli1, T. Ferraro1, G. Pollio1, D. Diamanti1, L. Magnoni1, S. Bernocco1, C. Scali1, S. Rasmussen4, H. B. Nielsen4, A.R. Bilia2, A. Karioti2, L. Millucci3, A. Caricasole1, D. Franceschini1.
Siena Biotech S.p.A., Strada del Petriccio e Belriguardo, 35. 53100, Siena, Italy. 2 University of Florence. Department of Pharmaceutical Science, Via Gino Capponi 9, 50121 Firenze, Italy. 3University of Siena. Dept. of Molecular Biology, Via Fiorentina 1, 53100 Siena, Italy. 4Center for Biological Sequence Analysis. Technical University of Denmark. Kemitorvet, Building 208. DK-2800 Lyngby, Denmark.
Siena Biotech S.p.A., Strada del Petriccio e Belriguardo, 35. 53100, Siena, Italy. 2 University of Florence. Department of Pharmaceutical Science, Via Gino Capponi 9, 50121 Firenze, Italy. 3University of Siena. Dept. of Molecular Biology, Via Fiorentina 1, 53100 Siena, Italy. 4Center for Biological Sequence Analysis. Technical University of Denmark. Kemitorvet, Building 208. DK-2800 Lyngby, Denmark.
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting the cognitive functions in the elderly. Beta-amyloid (ßA) toxicity has been hypothesised as central mechanism in AD development considering the high presence in the brain of AD patients of ßA plaques, which is a hallmark of this pathology.
The present study aimed to analyse the gene expression changes in an in vitro model of AD pathology, possibly expanding the knowledge on pathways involved in ßA-related neuronal death.
Two amyloids, ßA 1-42 and 25-35 were used to induce toxicity in rat cortical neurons and the phenotypic changes were revealed by biochemical and imaging-based methods. As reference compounds of the models two small molecules able to counteract ßA’s toxicity were chosen after testing a small panel of compounds owning neuroprotective characteristic. mRNA’s changes were analysed by microArray for checking the genes differentially regulated in these paradigms. The top 200 regulated genes were selected and their possible commitment in pathways neuroprotection analysed. Compounds were able revert gene changes in several clusters of genes. Analysis is still ongoing, in this work only preliminary results in the neurons ßA 25-35-treated are shown.
The present study aimed to analyse the gene expression changes in an in vitro model of AD pathology, possibly expanding the knowledge on pathways involved in ßA-related neuronal death.
Two amyloids, ßA 1-42 and 25-35 were used to induce toxicity in rat cortical neurons and the phenotypic changes were revealed by biochemical and imaging-based methods. As reference compounds of the models two small molecules able to counteract ßA’s toxicity were chosen after testing a small panel of compounds owning neuroprotective characteristic. mRNA’s changes were analysed by microArray for checking the genes differentially regulated in these paradigms. The top 200 regulated genes were selected and their possible commitment in pathways neuroprotection analysed. Compounds were able revert gene changes in several clusters of genes. Analysis is still ongoing, in this work only preliminary results in the neurons ßA 25-35-treated are shown.