TSPO, a Mitochondrial Outer Membrane Protein, Controls Ethanol-Related Behaviors in

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Alcohol use disorders (AUDs) affect millions of patients worldwide and result in high social and economic burdens. Although environmental factors are involved, there are clear genetic components to AUDs. Both the acute sedating effect of alcohol exposure and alcohol tolerance contribute to long term risk for alcohol dependence and addiction. Yet the genetic etiology of AUDs remains to be determined. The mitochondria play a central role in ethanol metabolism and are important in many aspects of cellular physiology such as REDOX and ROS regulation, and apoptosis. The mitochondrial outer membrane translocator protein 18 kDa (TSPO) binds the benzodiazepines and perhaps other addictive drugs, and thus may play a role in AUDs. Since Drosophila is a well-established model for ethanol-related behaviors, we have developed systems for manipulating the Drosophila tspo gene and protein. With these systems, we have discovered that neuronal TSPO controls sensitivity to ethanol sedation via ROS and caspase-mediated signaling and that systemic TSPO levels are important in the development of tolerance to repeated ethanol exposure. Given the variety of known TSPO ligands, and the common mechanisms of various abusive substances, our studies suggest that TSPO might be a promising target to combat alcoholism as well as addiction to other drugs.

Vyšlo v časopise: TSPO, a Mitochondrial Outer Membrane Protein, Controls Ethanol-Related Behaviors in. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005366
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005366

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