VDAC1 and Alzheimer’s

Dr. Weeks’ Comment:  VDAC1 is not just for cancer  – it remedies inflammatory illnesses exacerbated by mitochondrial sluggishness like Alzheimer’s.

 

 2018 May;131:87-101. doi: 10.1016/j.phrs.2018.03.010. Epub 2018 Mar 15.

VDAC1, mitochondrial dysfunction, and Alzheimer’s disease.

Abstract

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. VDAC1is 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 VDAC1triggers 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.

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Dr. Weeks’ Comment:  VDAC1 is not just for cancer  – it remedies inflammatory illnesses exacerbated by mitochondrial sluggishness like Alzheimer’s.   Pharmacol Res. 2018 May;131:87-101. doi: 10.1016/j.phrs.2018.03.010. Epub 2018 Mar 15. VDAC1, mitochondrial dysfunction, and Alzheimer’s disease. Shoshan-Barmatz V1, Nahon-Crystal E2, Shteinfer-Kuzmine A2, Gupta R2. Abstract Alzheimer’s disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β…
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