Is Voltage-Dependent Anion Channel a Major Player in Neurodegenerative Diseases?

The family of voltage-dependent anion channels (VDAC) comprises three isoforms (VDAC-1, VDAC-2, VDAC-3). VDAC has been extensively described as localized in the outer mitochondrial membrane where it is involved in the exchange of ions, metabolites and ATP/ADP between mitochondria and cytosol. VDAC interacts with disease specific proteins and thus regulates the mitochondrial function and controls the cellular energy resources explaining its involvement in cell death and apoptosis. In addition, VDAC-1 and -2 can also be found at other cellular locations such as in the sarcoplasmic reticulum, in the endoplasmic reticulum as well as in the plasma membrane. Through single channel pore regulation, oligomerization or changed expression levels VDAC is involved in different neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease and others. Here, we critically summarize current discussions about VDAC as a common key player for these diseases. We suggest that VDAC acts as a transmembrane multifunctional regulatory protein which might serve as a pharmacological target for the development of novel drugs against neurodegenerative diseases such application of recombinant antibody technology.