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. T., Pieroni, L., Diamantini, A., Battistini, L., Longone, P., Spalloni, A., De Laurenzi, V., Bernardini, S., Federici, G., Urbani, A., Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol, <<JOURNAL OF PROTEOMICS>>, 2012; 75 (4): 1440-53-1453. [doi:10.1016/j.jprot.2011.11.014] [http://hdl.handle.net/10807/79516]

Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol

Urbani, Andrea
Ultimo
2012

Abstract

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.
2012
Inglese
D'Alessandro, A., D'Aguanno, S., Cencioni, M. T., Pieroni, L., Diamantini, A., Battistini, L., Longone, P., Spalloni, A., De Laurenzi, V., Bernardini, S., Federici, G., Urbani, A., Protein repertoire impact of Ubiquitin-Proteasome System impairment: insight into the protective role of beta-estradiol, <<JOURNAL OF PROTEOMICS>>, 2012; 75 (4): 1440-53-1453. [doi:10.1016/j.jprot.2011.11.014] [http://hdl.handle.net/10807/79516]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/79516
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