VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis
Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells...
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doaj-7273b804030a434d96de954f90d7f3052020-11-24T22:24:28ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462018-04-01610.3389/fchem.2018.00108372045VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in ApoptosisAndrea Magrì0Andrea Magrì1Simona Reina2Simona Reina3Vito De Pinto4Section of Molecular Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, ItalySection of Biology and Genetics, Department of Biomedicine and Biotechnology, National Institute for Biomembranes and Biosystems, Section of Catania, Catania, ItalySection of Molecular Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, ItalySection of Biology and Genetics, Department of Biomedicine and Biotechnology, National Institute for Biomembranes and Biosystems, Section of Catania, Catania, ItalySection of Biology and Genetics, Department of Biomedicine and Biotechnology, National Institute for Biomembranes and Biosystems, Section of Catania, Catania, ItalyCancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies. Located in the outer mitochondrial membrane, VDAC forms channels that control the flux of ions and metabolites across the mitochondrion thus mediating the organelle's cross-talk with the rest of the cell. Furthermore, the interaction with both pro-apoptotic and anti-apoptotic factors makes VDAC a gatekeeper for mitochondria-mediated cell death and survival signaling pathways. Unfortunately, the lack of an evident druggability of this protein, since it has no defined binding or active sites, makes the quest for VDAC interacting molecules a difficult tale. Pharmacologically active molecules of different classes have been proposed to hit cancer and neurodegeneration. In this work, we provide an exhaustive and detailed survey of all the molecules, peptides, and microRNAs that exploit VDAC in the treatment of the two examined classes of pathologies. The mechanism of action and the potential or effectiveness of each compound are discussed.http://journal.frontiersin.org/article/10.3389/fchem.2018.00108/fullmitochondriaapoptosisVDACpeptidesoligosmicroRNAs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrea Magrì Andrea Magrì Simona Reina Simona Reina Vito De Pinto |
spellingShingle |
Andrea Magrì Andrea Magrì Simona Reina Simona Reina Vito De Pinto VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis Frontiers in Chemistry mitochondria apoptosis VDAC peptides oligos microRNAs |
author_facet |
Andrea Magrì Andrea Magrì Simona Reina Simona Reina Vito De Pinto |
author_sort |
Andrea Magrì |
title |
VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis |
title_short |
VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis |
title_full |
VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis |
title_fullStr |
VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis |
title_full_unstemmed |
VDAC1 as Pharmacological Target in Cancer and Neurodegeneration: Focus on Its Role in Apoptosis |
title_sort |
vdac1 as pharmacological target in cancer and neurodegeneration: focus on its role in apoptosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Chemistry |
issn |
2296-2646 |
publishDate |
2018-04-01 |
description |
Cancer and neurodegeneration are different classes of diseases that share the involvement of mitochondria in their pathogenesis. Whereas the high glycolytic rate (the so-called Warburg metabolism) and the suppression of apoptosis are key elements for the establishment and maintenance of cancer cells, mitochondrial dysfunction and increased cell death mark neurodegeneration. As a main actor in the regulation of cell metabolism and apoptosis, VDAC may represent the common point between these two broad families of pathologies. Located in the outer mitochondrial membrane, VDAC forms channels that control the flux of ions and metabolites across the mitochondrion thus mediating the organelle's cross-talk with the rest of the cell. Furthermore, the interaction with both pro-apoptotic and anti-apoptotic factors makes VDAC a gatekeeper for mitochondria-mediated cell death and survival signaling pathways. Unfortunately, the lack of an evident druggability of this protein, since it has no defined binding or active sites, makes the quest for VDAC interacting molecules a difficult tale. Pharmacologically active molecules of different classes have been proposed to hit cancer and neurodegeneration. In this work, we provide an exhaustive and detailed survey of all the molecules, peptides, and microRNAs that exploit VDAC in the treatment of the two examined classes of pathologies. The mechanism of action and the potential or effectiveness of each compound are discussed. |
topic |
mitochondria apoptosis VDAC peptides oligos microRNAs |
url |
http://journal.frontiersin.org/article/10.3389/fchem.2018.00108/full |
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