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Russell AE, Doll DN, Sarkar SN, et al. TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induced Neurotoxicity. J Clin Cell Immunol. 2016;7(6)doi: 10.4172/2155-9899.1000467.
Russell, A. E., Doll, D. N., Sarkar, S. N., & Simpkins, J. W. (2016). TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induced Neurotoxicity. Journal of clinical & cellular immunology, 7(6), . https://doi.org/10.4172/2155-9899.1000467
Russell, Ashley E, et al. "TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induced Neurotoxicity." Journal of clinical & cellular immunology vol. 7,6 (2016). doi: https://doi.org/10.4172/2155-9899.1000467
Russell AE, Doll DN, Sarkar SN, Simpkins JW. TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induced Neurotoxicity. J Clin Cell Immunol. 2016 Dec;7(6). doi: 10.4172/2155-9899.1000467. Epub 2016 Nov 14. PMID: 28652929; PMCID: PMC5482413.
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J Clin Cell Immunol. 2016 Dec;7(6). doi: 10.4172/2155-9899.1000467. Epub 2016 Nov 14.

TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induced Neurotoxicity.

Journal of clinical & cellular immunology

Ashley E Russell, Danielle N Doll, Saumyendra N Sarkar, James W Simpkins

Affiliations

  1. Physiology & Pharmacology, Center for Basic and Translational Stroke Research, Blanchett Rockefeller Neuroscience Institute, West Virginia University, Morgantown, West Virginia, USA.

PMID: 28652929 PMCID: PMC5482413 DOI: 10.4172/2155-9899.1000467

Abstract

This short communication describes our research which demonstrates that TNF-α causes a rapid decline in mitochondrial function, leading to neuronal cell death. As such, this neurotoxic proinflammatory cytokine may play a role in brain damage from stroke and neurodegeneration in chronic conditions such as Alzheimer's disease (AD) and Parkinson's disease. We have extended this initial observation by demonstrating that TNF-α stimulates a microRNA (miR-34a) which we have shown reduces five key proteins in the mitochondrial electron transport chain through base-pair complementarity. miR-34a is increased in affected brain regions of Alzheimer's patients and transgenic AD mouse models. We have further shown that oligomeric amyloid beta 42 (oAβ42) stimulates miR-34a. Collectively, these data suggest that TNF-α, oAβ42, and miR-34a participate in a vicious cycle, resulting in mitochondrial dysfunction, which is critical to the neuropathology of AD.

Keywords: Alzheimer’s disease; Electron transport proteins; Mitochondria; Oligomeric Aβ; Stroke; TNF-α; microRNA-34a

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