The Ubiquitin-Proteasome System (UPS) and the Autophagy-Lysosome Pathways (ALP) are key mechanisms for cellular homeostasis sustenance and protein clearance. A wide number of Neurodegenerative Diseases (NDs) are tied with UPS impairment and have been also described as proteinopathies caused by aggregate-prone proteins, not efficiently removed by proteasome. Despite the large knowledge on proteasome biological role, molecular mechanisms associated with its impairment are still blur. We have pursued a comprehensive proteomic investigation to evaluate the phenotypic rearrangements in protein repertoires associated with a UPS blockage. Different functional proteomic approaches have been employed to tackle UPS impairment impact on human NeuroBlastoma (NB) cell lines responsive to proteasome inhibition by Epoxomicin. 2-Dimensional Electrophoresis (2-DE) separation combined with Mass Spectrometry and Shotgun Proteomics experiments have been employed to design a thorough picture of protein profile. Unsupervised meta-analysis of the collected proteomic data revealed that all the identified proteins relate each other in a functional network centered on beta-estradiol. Moreover we showed that treatment of cells with beta-estradiol resulted in aggregate removal and increased cell survival due to activation of the autophagic pathway. Our data may provide the molecular basis for the use of beta-estradiol in neurodegenerative disorders by induction of protein aggregate removal.
D'Alessandro, A., D'Aguanno, S., Cencioni, M., Pieroni, L., Diamantini, A., Battistini, L., et al. (2012). Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol. JOURNAL OF PROTEOMICS, 75(4), 1440-1453 [10.1016/j.jprot.2011.11.014].
Tipologia: | Articolo su rivista | |
Citazione: | D'Alessandro, A., D'Aguanno, S., Cencioni, M., Pieroni, L., Diamantini, A., Battistini, L., et al. (2012). Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol. JOURNAL OF PROTEOMICS, 75(4), 1440-1453 [10.1016/j.jprot.2011.11.014]. | |
Lingua: | English | |
Settore Scientifico Disciplinare: | Settore BIO/12 | |
Revisione (peer review): | Esperti anonimi | |
Tipo: | Articolo | |
Rilevanza: | Rilevanza internazionale | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.jprot.2011.11.014 | |
Stato di pubblicazione: | Pubblicato | |
Data di pubblicazione: | 2-feb-2012 | |
Titolo: | Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol | |
Autori: | ||
Autori: | D'Alessandro, A; D'Aguanno, S; Cencioni, M; Pieroni, L; Diamantini, A; Battistini, L; Longone, P; Spalloni, A; De Laurenzi, V; Bernardini, S; Federici, G; Urbani, A | |
Appare nelle tipologie: | 01 - Articolo su rivista |
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