Translocator protein: Wikis


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translocator protein (18kDa)
External IDs OMIM109610 MGI88222 HomoloGene574 GeneCards: TSPO Gene
Species Human Mouse
Entrez 706 12257
Ensembl ENSG00000100300 ENSMUSG00000041736
UniProt P30536 P50637
RefSeq (mRNA) NM_007311 NM_009775
RefSeq (protein) NP_009295 NP_033905
Location (UCSC) Chr 22:
41.88 - 41.89 Mb
Chr 15:
83.39 - 83.4 Mb
PubMed search [1] [2]

Translocator protein (TSPO) is an 18 kDa protein of the outer mitochondrial membrane. It was first described as peripheral benzodiazepine receptor (PBR), a secondary binding site for diazepam, but subsequent research has found the receptor to be expressed throughout the body and brain.[1] In humans, the translocator protein is encoded by the TSPO gene.[2][3]



TSPO has many proposed functions,[4] the most studied of these are:

Tissue distribution

Peripheral benzodiazepine receptors are found in many regions of the body including the human iris/ciliary-body.[7] Other tissues where peripheral benzodiazepine receptors are found include the heart, liver, adrenal and testis, as well as hemopoietic and lymphatic cells.[8] In lymphatic tissues, they modulate apoptosis of thymocytes via reduction of mitochondrial transmembrane potential.[9] PBRs have many other actions on immune cells including modulation of oxidative bursts by neutrophils and macrophages, and inhibition of macrophage secretion of cytokines inhibition of the proliferation of lymphoid cells and secretion of cytokines by macrophages.[10] "Peripheral" benzodiazepine receptors are also found in the brain, although only at around a quarter the expression levels of the "central" benzodiazepine receptors.[11]

Therapeutic Applications

TSPO has been shown to be involved in a number of processes such as inflammation,[12] and TSPO ligands may be useful anti-cancer drugs.[13][14] Activation of TSPO is also required for steroidogenesis to take place,[15][16] and this is particularly important for the production of neuroactive steroids such as allopregnanolone in the brain. This makes some TSPO ligands such as emapunil (XBD-173) useful as potential anxiolytics which may have less side effects than traditional benzodiazepine-type drugs.[17][18][19][20]


Ligands of the TSPO are very useful for imaging of inflammation, for example, the ligand [3H]-PK-11195 has been used in receptor autoradiography to study neuroinflammation following brain injury.

Selective Ligands



  • Anthralin - 16kDa polypeptide, binds to both TSPO receptor and dihydropyridine-sensitive calcium channels with high affinity.[21]
  • Diazepam binding inhibitor (DBI) - 11kDa neuropeptide, potent agonist for TSPO receptor and stimulates steroidogenesis in vivo,[22][23][5] also negative allosteric modulator of benzodiazepine-sensitive GABAA receptors.[24]
  • DBI 17-50 fragment - active processing product of DBI


  • PK-11195 - potent and selective antagonist for both rat and human forms of TSPO.
  • Ro5-4864 - original ligand with which TSPO receptor was characterised, now less used due to inter-species differences in binding affinity. Sedative yet also convulsant and anxiogenic in mice.[25]


  1. ^ Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapère JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang MR, Gavish M (August 2006). "Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function". Trends Pharmacol. Sci. 27 (8): 402–9. doi:10.1016/ PMID 16822554.  
  2. ^ Chang YJ, McCabe RT, Rennert H, Budarf ML, Sayegh R, Emanuel BS, Skolnick P, Strauss JF (1992). "The human "peripheral-type" benzodiazepine receptor: regional mapping of the gene and characterization of the receptor expressed from cDNA". DNA Cell Biol. 11 (6): 471–80. PMID 1326278.  
  3. ^ Riond J, Mattei MG, Kaghad M, Dumont X, Guillemot JC, Le Fur G, Caput D, Ferrara P (January 1991). "Molecular cloning and chromosomal localization of a human peripheral-type benzodiazepine receptor". Eur. J. Biochem. 195 (2): 305–11. doi:10.1111/j.1432-1033.1991.tb15707.x. PMID 1847678.  
  4. ^ Casellas P, Galiegue S, Basile AS (2002). "Peripheral benzodiazepine receptors and mitochondrial function". Neurochem Int 40 (6): 475–86. doi:10.1016/S0197-0186(01)00118-8. PMID 11850104.  
  5. ^ a b Papadopoulos V, Amri H, Boujrad N, Cascio C, Culty M, Garnier M, Hardwick M, Li H, Vidic B, Brown AS, Reversa JL, Bernassau JM, Drieu K (January 1997). "Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis". Steroids 62 (1): 21–8. PMID 9029710.  
  6. ^ Frank W, Baar KM, Qudeimat E, Woriedh M, Alawady A, Ratnadewi D, Gremillon L, Grimm B, Reski R (September 2007). "A mitochondrial protein homologous to the mammalian peripheral-type benzodiazepine receptor is essential for stress adaptation in plants". Plant J. 51 (6): 1004–18. doi:10.1111/j.1365-313X.2007.03198.x. PMID 17651369.  
  7. ^ Valtier D, Malgouris C, Gilbert JC, Guicheney P, Uzan A, Gueremy C, Le Fur G, Saraux H, Meyer P (June 1987). "Binding sites for a peripheral type benzodiazepine antagonist ([3H]PK 11195) in human iris". Neuropharmacology 26 (6): 549–52. PMID 3037422.  
  8. ^ Woods MG, Williams DC (1996). Multiple forms and locations for the peripheral-type benzodiazepine receptor. 52. 1805–1814. doi:10.1016/S0006-2952(96)00558-8.  
  9. ^ Tanimoto Yutaka; Onishi, Yoshiaki (1999). "Benzodiazepine Receptor Agonists Modulate Thymocyte Apoptosis Through Reduction of the Mitochondrial Transmembrane Potential" (PDF). Jpn J Pharmacol. 79: 177–183. doi:10.1254/jjp.79.177. PMID 10202853.  
  10. ^ Pawlikowski M (1993). "Immunomodulating effects of peripherally acting benzodiazepines". Academic press. New York: In Peripheral Benzodiazepine Receptors. pp. 125–135.  
  11. ^ Marangos PJ, Patel J, Boulenger JP, Clark-Rosenberg R (July 1982). "Characterization of peripheral-type benzodiazepine binding sites in brain using [3H]Ro 5-4864". Molecular Pharmacology 22 (1): 26–32. PMID 6289073.  
  12. ^ Chen MK, Guilarte TR (April 2008). "Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair". Pharmacology & Therapeutics 118 (1): 1–17. doi:10.1016/j.pharmthera.2007.12.004. PMID 18374421.  
  13. ^ Santidrián AF, Cosialls AM, Coll-Mulet L, Iglesias-Serret D, de Frias M, González-Gironès DM, Campàs C, Domingo A, Pons G, Gil J (December 2007). "The potential anticancer agent PK11195 induces apoptosis irrespective of p53 and ATM status in chronic lymphocytic leukemia cells". Haematologica 92 (12): 1631–8. doi:10.3324/haematol.11194. PMID 18055986.  
  14. ^ Kugler W, Veenman L, Shandalov Y, Leschiner S, Spanier I, Lakomek M, Gavish M (2008). "Ligands of the mitochondrial 18 kDa translocator protein attenuate apoptosis of human glioblastoma cells exposed to erucylphosphohomocholine". Cellular Oncology : the Official Journal of the International Society for Cellular Oncology 30 (5): 435–50. PMID 18791274.  
  15. ^ Veenman L, Papadopoulos V, Gavish M (2007). "Channel-like functions of the 18-kDa translocator protein (TSPO): regulation of apoptosis and steroidogenesis as part of the host-defense response". Current Pharmaceutical Design 13 (23): 2385–405. PMID 17692008.  
  16. ^ Falchi AM, Battetta B, Sanna F, Piludu M, Sogos V, Serra M, Melis M, Putzolu M, Diaz G (August 2007). "Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands". Neuropharmacology 53 (2): 318–29. doi:10.1016/j.neuropharm.2007.05.016. PMID 17631921.  
  17. ^ Mealy NE, Bayés M, Lupone B, Balcells M. Update 2006: Psychiatric Disorders. Drugs of the Future. 2006;31(3): 259.
  18. ^ Da Settimo F, Simorini F, Taliani S, La Motta C, Marini AM, Salerno S, Bellandi M, Novellino E, Greco G, Cosimelli B, Da Pozzo E, Costa B, Simola N, Morelli M, Martini C (September 2008). "Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis". Journal of Medicinal Chemistry 51 (18): 5798–806. doi:10.1021/jm8003224. PMID 18729350.  
  19. ^ Taliani S, Da Settimo F, Da Pozzo E, Chelli B, Martini C (September 2009). "Translocator Protein Ligands as Promising Therapeutic Tools for Anxiety Disorders". Current Medicinal Chemistry. PMID 19548867.  
  20. ^ Rupprecht R, Rammes G, Eser D, Baghai TC, Schüle C, Nothdurfter C, Troxler T, Gentsch C, Kalkman HO, Chaperon F, Uzunov V, McAllister KH, Bertaina-Anglade V, La Rochelle CD, Tuerck D, Floesser A, Kiese B, Schumacher M, Landgraf R, Holsboer F, Kucher K (June 2009). "Translocator Protein (18 kD) as Target for Anxiolytics Without Benzodiazepine-Like Side Effects". Science (New York, N.Y.). doi:10.1126/science.1175055. PMID 19541954.  
  21. ^ Gavish M, Bachman I, Shoukrun R, Katz Y, Veenman L, Weisinger G, Weizman A (December 1999). "Enigma of the peripheral benzodiazepine receptor". Pharmacological Reviews 51 (4): 629–50. PMID 10581326.  
  22. ^ Costa E, Auta J, Guidotti A, Korneyev A, Romeo E (June 1994). "The pharmacology of neurosteroidogenesis". The Journal of Steroid Biochemistry and Molecular Biology 49 (4-6): 385–9. PMID 8043504.  
  23. ^ Garnier M, Boujrad N, Ogwuegbu SO, Hudson JR, Papadopoulos V (September 1994). "The polypeptide diazepam-binding inhibitor and a higher affinity mitochondrial peripheral-type benzodiazepine receptor sustain constitutive steroidogenesis in the R2C Leydig tumor cell line". The Journal of Biological Chemistry 269 (35): 22105–12. PMID 8071335.  
  24. ^ Bormann J, Ferrero P, Guidotti A, Costa E (1985). "Neuropeptide modulation of GABA receptor C1- channels". Regulatory Peptides. Supplement 4: 33–8. PMID 2414820.  
  25. ^ Pellow S, File SE (July 1984). "Behavioural actions of Ro 5-4864: a peripheral-type benzodiazepine?". Life Sciences 35 (3): 229–40. PMID 6087055.  

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