VDAC1, mitochondrial dysfunction, and Alzheimer's disease

Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta

Research output: Contribution to journalReview articlepeer-review

135 Scopus citations


Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis. VDAC1 is a multi-functional protein, expressed in the mitochondria and other cell compartments, including the plasma membrane. The protein regulates the main metabolic and energetic functions of the cell, including Ca2+ homeostasis, oxidative stress, and mitochondria-mediated apoptosis. VDAC1 represents a hub protein that interacts with over 150 other proteins including phosphorylated tau, Aβ and γ-secretase, and participates in their toxicity. The high levels of VDAC1 demonstrated post-mortem in the brains of AD patients and in amyloid precursor protein (APP) transgenic mice prompted the hypothesis that the protein may be associated with neuronal cell destruction since over-expression of VDAC1 triggers cell death. Thus, targeting mitochondrial dysfunction via VDAC1, to prevent this pro-apoptotic activity, could represent a novel strategy for inhibiting cell death. In addition, the review also discusses possible VDAC1 involvement in the link between AD and diabetes and the inverse association between cancer and AD.

Original languageEnglish
Pages (from-to)87-101
Number of pages15
JournalPharmacological Research
StatePublished - 1 May 2018


  • Alzheimer's disease
  • Apoptosis
  • Metabolism
  • Mitochondria
  • Voltage-dependent anion channel 1

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'VDAC1, mitochondrial dysfunction, and Alzheimer's disease'. Together they form a unique fingerprint.

Cite this