Affiliation:
1. Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy
Abstract
Background:
The Voltage Dependent Anion Channel (VDAC) proteins represent
the most important pore-forming proteins of the mitochondrial outer membrane, directly involved
in metabolism and apoptosis regulation. Literature has highlighted a key role of
VDACs in mitochondrial dysfunction typical of many neurodegenerative disorders. In particular,
the principal isoform VDAC1 represents the main mitochondrial docking site of many
misfolded proteins, such as amyloid β and Tau in Alzheimer's disease, α-synuclein in Parkinson's
disease and several SOD1 mutants in Amyotrophic Lateral Sclerosis. The interaction of
misfolded proteins with VDAC1 has a strong impact on both cellular bioenergetics and apoptosis'
pathways alteration. Therefore, VDACs represent a promising therapeutic target in neurodegeneration.
Objective:
This review summarizes the roles of VDAC isoforms, and particularly of VDAC1,
in the most common neurological disorders and analyzes in detail molecules and peptides
available so far, able to interact and modulate VDAC1 in any considered pathological condition.
Conclusion:
This review offers a description of the most promising therapeutic strategies acting
on VDAC1, for the treatment of neurodegenerative diseases.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology,Molecular Medicine,Drug Discovery,Biochemistry,Organic Chemistry
Cited by
57 articles.
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