The Potential Role of Voltage-Dependent Anion Channel in the Treatment of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease second only to Alzheimer’s disease in terms of prevalence. Previous studies have indicated that the occurrence and progression of PD are associated with mitochondrial dysfunction. Mitochondrial dysfunction is one of the most important causes for apoptosis of dopaminergic neurons. Therefore, maintaining the stability of mitochondrial functioning is a potential strategy in the treatment of PD. Voltage-dependent anion channel (VDAC) is the main component in the outer mitochondrial membrane, and it participates in a variety of biological processes. In this review, we focus on the potential roles of VDACs in the treatment of PD. We found that VDACs are involved in PD by regulating apoptosis, autophagy, and ferroptosis. VDAC1 oligomerization, VDACs ubiquitination, regulation of mitochondrial permeability transition pore (mPTP) by VDACs, and interaction between VDACs and α-synuclein (α-syn) are all promising methods for the treatment of PD. We proposed that inhibition of VDAC1 oligomerization and promotion of VDAC1 ubiquitination as an effective approach for the treatment of PD. Previous studies have proven that the expression of VDAC1 has a significant change in PD models. The expression levels of VDAC1 are decreased in the substantia nigra (SN) of patients suffering from PD compared with the control group consisting of normal individuals by using bioinformatics tools. VDAC2 is involved in PD mainly through the regulation of apoptosis. VDAC3 may have a similar function to VDAC1. It can be concluded that the functional roles of VDACs contribute to the therapeutic strategy of PD.

Acyl-CoA synthetase 4 modulates mitochondrial function in breast cancer cells

“…Mitochondrial Complex III accepts electrons both from complex I and complex II through ubiquinone and increased activity of this complex has been reported in cancer [ [37] , [38] , [39] ]. In turn, VDAC1 is the most extensively characterized and abundant isoform of the VDAC protein family, and it has been implicated in pathologies such as cancer or neurodegenerative diseases [ [40] , [41] , [42] ]. Our results showed a significant increase in Complex III ( Fig.…”

Neuronal Protection by Ha-RAS-GTPase Signaling through Selective Downregulation of Plasmalemmal Voltage-Dependent Anion Channel-1

“…In a cellular model of Parkinson’s disease, the dopaminergic cell line SH-SY5Y was exposed to the mitochondrial complex-1 inhibitor rotenone leading to increased VDAC-1 levels [ 65 ], while in post-mortal brain tissue, VDAC-1 levels are clearly reduced [ 35 ]. A potential involvement of VDAC-1 is also proposed for patients with autism where antibodies against the hexokinase-1 (HK-1) have been found [ 66 ].…”

“…In post mortem brains of Alzheimer’s disease patients, VDAC-1 is overexpressed [ 33 ], and therefore, prodromal Alzheimer’s disease might be recognized by VDAC-1 overexpression as a biomarker [ 34 ]. There is broad evidence showing the participation of VDAC-1 in Parkinson’s disease via its interaction with α-synuclein mediating its transport via the pore-regulating Ca 2+ -homeostasis [ 35 ], altogether providing evidence for the involvement of VDAC-1 in neurodegenerative diseases [ 34 , 36 ].…”

Ferroptosis and its current progress in gastric cancer

“…VDAC, known as the voltage-dependent anion channel, belongs to the eukaryotic mitochondrial porin protein family. It constitutes a significant portion of the outer mitochondrial membrane and regulates the exchange of substances between the mitochondria and the cytoplasm ( He et al, 2022 ). In cancer cells, elevated levels of free tubulin close VDAC to decrease the mitochondrial membrane potential.…”