TSPO

2022-09-04: reference:

Translocator Protein (TSPO) #

• Located in outer mithcondrial protein.
• Possible interactions with StAR; stimulates neurosteroid synthesis, i.e. Allopregnanolone.
• Biomarker of cardiovascular disease
• Binds benzodiazepines; Pax says TPSO reduces the density of GABAergic interneurons.
• Diazepam binding inhibitor (DBI) - 11kDa neuropeptide, potent agonist for TSPO receptor and stimulates steroidogenesis in vivo, also negative allosteric modulator of benzodiazepine-sensitive GABAA receptors
• Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands
  • TSPO ligands induce changes in the distribution of intracellular cholesterol in astrocytes and fibroblasts
• Ligand for Translocator Protein Reverses Pathology in a Mouse Model of Alzheimer’s Disease
• Channel-Like Functions of the 18-kDa Translocator Protein (TSPO): Regulation of Apoptosis and Steroidogenesis as Part of the Host-Defense Response
  • ProtoPorphyrin IX is a ligand.
• Agonism leads to mitochondrial inflammation

Benzodiazepenes #

• Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO)
  • https://neurosciencenews.com/anxiety-drugs-cognition-20932/
    • TSPO knockout mice do not experience the microglial remodeling seen from diazepam, which binds to both the Benzodiazepine site and TSPO, unlike something like clonazepam.
      • Diazepam binds to microglia rather than neurons or something?
• Enhancing neurosteroid synthesis–relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines
  • 
    • Etifoxine had the lowest binding affinity, yet was the most potent enhancer of neurosteroidogenesis.