Targeting PPAR isoforms following CNS injury.

Abstract:

: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.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Yonutas HM,Sullivan PG

doi

10.2174/1389450111314070003

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

733-42

issue

7

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-20130427-1

journal_volume

14

pub_type

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