Search results for "Hsp90"

Principal component analysis on molecular descriptors as an alternative point of view in the search of new Hsp90 inhibitors

2009

Inhibiting a protein that regulates multiple signal transduction pathways in cancer cells is an attractive goal for cancer therapy. Heat shock protein 90 (Hsp90) is one of the most promising molecular targets for such an approach. In fact, Hsp90 is a ubiquitous molecular chaperone protein that is involved in folding, activating and assembling of many key mediators of signal transduction, cellular growth, differentiation, stress-response and apoptothic pathways. With the aim to analyze which molecular descriptors have the higher importance in the binding interactions of these classes, we first performed molecular docking experiments on the 187 Hsp90 inhibitors included in the BindingDB, a pu…

ESPRESSIONE DI VEGF, HSP90 E Bip/GRP78 E RICORRENZA DI CARCINOMA EPATOCELLULARE DOPO TRAPIANTO DI FEGATO

Background and aims Liver transplantation (LT) for hepatocellular carcinoma (HCC) is a satisfactory therapeutic choice in patients with “early HCC” selected according to Milan criteria. However, the risk of HCC recurrence after LT is about 7-10% at five years and markers which can predict recurrence are still lacking. We investigated in HCC samples and LC surrounding tissues the significance of VEGF, HSP90, and Bip/GRP78 expression in patients with HCC who underwent LT in a western transplantation center and their possible role as markers of recurrence. Background and aims Liver transplantation (LT) for hepatocellular carcinoma (HCC) is a satisfactory therapeutic choice in patients with “ea…

VEGFR-2, HSP90 and GRP78/BiP expression and HCC recurrence after Liver Transplantation

2018

Introduction Liver transplantation (LT) for hepatocellular carcinoma (HCC) is a satisfactory therapeutic choice in patients with “early HCC” selected according to Milan criteria. However, the risk of HCC recurrence after LT is about 7-20% at five years and molecular markers which can predict recurrence are still lacking. We investigated in HCC samples and LC surrounding tissues the significance of VEGFR-2, HSP90, and GRP78/BiP expression in patients with HCC who underwent LT in a western transplantation center and their possible role as molecular markers of recurrence. Methods 42 patients (35 M, 7 F) with early HCC who underwent LT between 2012 and 2013 were enrolled. The tumor recurrence r…

Hsp90 dictates viral sequence space by balancing the evolutionary tradeoffs between protein stability, aggregation and translation rate

2017

AbstractAcquisition of mutations is central to evolution but the detrimental effects of most mutations on protein folding and stability limit protein evolvability. Molecular chaperones, which suppress aggregation and facilitate polypeptide folding, are proposed to promote sequence diversification by buffering destabilizing mutations. However, whether and how chaperones directly control protein evolution remains poorly understood. Here, we examine the effect of reducing the activity of the key eukaryotic chaperone Hsp90 on poliovirus evolution. Contrary to predictions of a buffering model, inhibiting Hsp90 increases population sequence diversity and promotes accumulation of mutations reducin…

Identification of the plant compound geraniin as a novel Hsp90 inhibitor

2013

Besides its function in normal cellular growth, the molecular chaperone heat shock protein 90 (Hsp90) binds to a large number of client proteins required for promoting cancer cell growth and/or survival. In an effort to discover new small molecules able to inhibit the Hsp90 ATPase and chaperoning activities, we screened, by a surface plasmon resonance assay, a small library including different plant polyphenols. The ellagitannin geraniin, was identified as the most promising molecule, showing a binding affinity to Hsp90α similar to that of 17-(allylamino)-17-demethoxygeldanamycin (17AGG). Geraniin was able to inhibit in vitro the Hsp90α ATPase activity in a dose−dependent manner, with an in…

HSP90 in ageing progression and ageing related diseases

2014

HSP90 activities decline during ageing. Noteworthy, HSP90 mediated retrotransposon silencing seems to have a key role in the maintenance of genome integrity. Furthermore, inhibition of HSP90 activities lead to cell senescence and apoptosis. Original bioinformatics analyses and literature data will be discussed in the light of the potential involvement of HSP90 in ageing progression and ageing related diseases.

Nuovi derivati 3,5-diaril-4,5-diidropirazolici come inibitori di HSP90

2008

Principal Component Analysis on molecular descriptors as alternative point of view in the search of new Hsp90 inhibitors

2008

PROGETTAZIONE, SINTESI E VALUTAZIONE BIOLOGICA DI NUOVI INIBITORI DI HSP90

2009

Protective role of heat shock proteins in Parkinson's disease.

2010

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Despite a large amount of research, the pathogenetic mechanism of these diseases has not yet been clarified. Abnormal protein folding, oxidative stress, mitochondrial dysfunction, and apoptotic mechanisms have all been reported as causes of neurodegenerative diseases in association with neuroinflammatory mechanisms which, by generating deleterious molecules, could promote the cascade of events leading to neurodegeneration. Heat shock proteins (HSPs) play a central role in preventing protein misfolding and inhibiting apoptotic activity, and represent a class of proteins potentially involve…