Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma

Exp Neurol. 2009 Sep;219(1):53-7. doi: 10.1016/j.expneurol.2009.04.016. Epub 2009 May 4.


Traumatic brain injury (TBI) induces physical, cognitive, and psychosocial deficits that affect millions of patients. TBI activates numerous cellular mechanisms and molecular cascades that produce detrimental outcomes, including neuronal death and loss of function. The mitochondrion is one of the major targets of TBI, as seen by increased mitochondrial activity in activated and proliferating microglia (due to high energy requirements and/or calcium overload) as well as increased reactive oxygen species, changes in mitochondrial permeability transition, release of cytochrome c, caspase activation, reduced ATP levels, and cell death in neurons. Translocator protein (TSPO) is an 18-kDa outer mitochondrial membrane protein that interacts with the mitochondria permeability transition pore and binds with high affinity to cholesterol and various classes of drug ligands, including some benzodiazepines such as 4'-chlorodiazepam (Ro5-4864). Although TSPO levels in the brain are low, they are increased after brain injury and inflammation. This finding has led to the proposed use of TSPO expression as a marker of brain injury and repair. TSPO drug ligands have been shown to participate in the control of mitochondrial respiration and function, mitochondrial steroid and neurosteroid formation, as well as apoptosis. This review and commentary will outline our current knowledge of the benefits of targeting TSPO for TBI treatment and the mechanisms underlying the neuroprotective effects of TSPO drug ligands in neurotrauma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology*
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism*
  • Brain Injuries / physiopathology*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Respiration / drug effects
  • Cell Respiration / physiology
  • Drug Design
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / physiopathology
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism*
  • Regeneration / drug effects
  • Regeneration / physiology


  • Receptors, GABA
  • TSPO protein, human