Interactions of VDAC with proteins involved in neurodegenerative aggregation: an opportunity for advancement on therapeutic molecules.

Interactions of VDAC with proteins involved in neurodegenerative aggregation: an opportunity for advancement on therapeutic molecules. Curr Med Chem. 2017 May 31;: Authors: Magrì A, Messina A Abstract 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. The recent 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. 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. Overall, this review offers a description of the most promising molecules acting on VDAC1 potentially usable in a new therapeutic strategy for the treatment of neurodegenerative disea...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research