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Necrostatin-1 mitigates mitochondrial dysfunction post-spinal cord injury.

Authors: Wang, Y  Wang, J  Yang, H  Zhou, J  Feng, X  Wang, H  Tao, Y 
Citation: Wang Y, etal., Neuroscience. 2015 Mar 19;289:224-32. doi: 10.1016/j.neuroscience.2014.12.061. Epub 2015 Jan 13.
Pubmed: (View Article at PubMed) PMID:25595990
DOI: Full-text: DOI:10.1016/j.neuroscience.2014.12.061

Necrostatin-1 (Nec-1) is an inhibitor of necroptosis, playing an important role in inhibition of pathological death in the central nervous system (CNS). Our earlier study suggests that Nec-1 protects the injured spinal cord. In this study, we found that Nec-1 reduces the elevated Ca(2+) concentration in mitochondria post-injury and preserves the remarkably decreased mitochondrial membrane potential (MMP) level post-spinal cord injury (SCI). It also increases the generation of adenosine triphosphate (ATP) by promoting the activity of mitochondrial respiratory chain complex I instead of other complexes, which are significantly decreased due to the injury. Nec-1 also inhibits the release of cytochrome c in the mitochondria and protects the spinal cord from mitochondrial swelling post-SCI. Nec-1 promotes mitochondrial biogenesis by up-regulating mitochondrial transcription factor A (Tfam), in accordance with the mtDNA content. It also inhibits the up-regulation of mitochondrial fusion genes Mnf1, Mnf2 within 6h post-injury and adjusts the abnormal expression of mitochondrial fission gene Fis1. All these results indicate the improvement of mitochondrial functions in injured spinal cord after the treatment of Nec-1. This research revealed the mechanisms of functional protection of Nec-1 by mitigating mitochondrial dysfunction post-SCI.


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CRRD Object Information
CRRD ID: 12437079
Created: 2017-01-27
Species: All species
Last Modified: 2017-01-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.