"TNF-α and Beyond: Rapid Mitochondrial Dysfunction Mediates TNF-α-Induc" by A E. Russell, D N. Doll et al.
 

Title

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

Document Type

Article

Publication Date

12-1-2016

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.

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