A major focus has developed for the discovery of proregenerative and neuroprotective therapeutic agents to
help the millions of Americans who receive a CNS injury annually. Tribulations have been encountered along the way due
to the complicated set of pathways that are initiated post-injury. To target this complicated multifaceted signaling cascade,
the most promising therapeutics target multiple pathways involved in the secondary injury cascade, such as neuroinflammation,
the generation of ROS and mitochondrial dysfunction. Compelling experimental data demonstrates that mitochondrial
dysfunction is a pivotal link in the neuropathological sequelae of brain injury. A group of PPAR agonists, specifically
rosiglitazone and pioglitazone, have shown an extreme amount of promise in the realm of drug discovery for
CNS injury due to their ability to increase functional recovery and decrease lesion volumes following injury. The therapeutic
effects of these PPAR agonists are thought to be a direct result of PPAR activity however new data is arising that
shows some of the effects may be independent of PPAR activity, targeting a novel mitochondrial protein called mitoNEET.
In this review, a thorough evaluation of the role of PPAR and mitoNEET in rosiglitazone and pioglitazone mediated
neuroprotection will be completed in order to shed light on the mechanism of a new possible therapeutic intervention
for CNS injury.
Keywords: Mitochondria, mitoNEET, traumatic brain injury, spinal cord injury, excitotoxicity, neuroinflammation.
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