Affinage

TSPO

Translocator protein · UniProt P30536

Length
169 aa
Mass
18.8 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TSPO is an outer mitochondrial membrane protein that functions as a regulator of mitochondrial bioenergetics and metabolic state rather than as an essential cholesterol transporter (PMID:26741196, PMID:25406832). Atomic-resolution structures define it as a tightly interacting dimer that adopts a rigid five-helix bundle when bound to ligands such as PK11195 but samples multiple conformations with local unfolding near the ligand-binding site in their absence, and that harbors an endogenous porphyrin-binding site whose cholesterol interaction is altered by the human Ala147Thr polymorphism (PMID:25635101, PMID:26394723, PMID:26551694). Genetic ablation shifts mitochondrial substrate utilization toward fatty acid oxidation and raises ROS without changing oxygen consumption (PMID:26741196), while loss of TSPO lowers ATP production and impairs OXPHOS and glycolysis in microglia (PMID:25406832, PMID:32695005); multiple knockout models show normal cholesterol transport, pregnenolone levels, and steroidogenesis, directly refuting the long-held essential steroidogenic role (PMID:25406832). Through this metabolic control, TSPO is required for microglial activation and phagocytic function, including amyloid-β clearance, and drives NOX1-dependent neurotoxic ROS in retinal phagocytes during neovascular degeneration (PMID:32695005, PMID:34340010, PMID:32483169). TSPO also governs hypothalamic tanycyte lipophagy and energy balance via an AMPK-dependent pathway and interacts with p62/SQSTM1 to modulate autophagy and Nrf2-dependent antioxidant signaling in tumor cells (PMID:31469345, PMID:36994647). Its expression is induced by neuronal activity in neurons, and diazepam acting through TSPO—not GABAA receptors—promotes microglial engulfment of dendritic spines (PMID:32398717, PMID:35228700). Pharmacologically, TSPO ligands stimulate mitochondrial neurosteroid (pregnenolone) synthesis and redistribute intracellular cholesterol (PMID:8411007, PMID:17631921).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1992 Medium

    Established that TSPO is not exclusively mitochondrial, with a plasma-membrane pool in steroidogenic adrenal cells, hinting at functions beyond the canonical mitochondrial location.

    Evidence Anti-peptide immunocytochemistry and confocal microscopy with 3D reconstruction in mouse adrenal cortex

    PMID:1332905

    Open questions at the time
    • Functional role of the plasma-membrane pool not defined
    • Single method, single lab
  2. 1993 Medium

    Linked TSPO pharmacology directly to mitochondrial neurosteroidogenesis by showing TSPO ligands stimulate pregnenolone formation, framing TSPO as a regulator of steroid synthesis.

    Evidence In vitro mitochondrial steroid synthesis assay in C6-2B glioma cells with radioligand displacement and SAR studies

    PMID:8411007

    Open questions at the time
    • Pharmacological correlation does not establish that TSPO protein is mechanistically required
    • No genetic loss-of-function control
  3. 2003 Medium

    Provided a signaling rationale for TSPO in steroidogenesis by identifying PAP7 as an AKAP bridging cAMP/PKA to TSPO-mediated cholesterol transport.

    Evidence Phage display, co-immunoprecipitation, antisense knockdown, and steroid production assay

    PMID:12943713

    Open questions at the time
    • Knockdown-based, later contradicted by knockout steroid phenotypes
    • Single lab
  4. 2002 Medium

    Loss-of-function (antisense) and competitive peptide antagonism supported a requirement for endogenous ligand–TSPO interaction in hormone-stimulated steroid formation.

    Evidence Antisense knockdown and phage-display peptide antagonist in MA-10 Leydig cells with steroid assays

    PMID:12530641

    Open questions at the time
    • Conclusions later challenged by viable steroid-normal knockout mice
    • Knockdown off-target effects not excluded
  5. 2004 Medium

    Showed that anti-proliferative effects of TSPO ligands in mesenchymal cells are PBR-independent, separating ligand pharmacology from receptor function.

    Evidence RNAi knockdown with proliferation, cell-cycle, and ERK/c-Jun assays in fibroblasts and fibrosarcoma cells

    PMID:15130769

    Open questions at the time
    • Negative result specific to mesenchymal cells
    • Does not address TSPO function in other lineages
  6. 2012 Medium

    Demonstrated TSPO ligands remodel intracellular cholesterol distribution and mitochondrial state, with GABAA-selective controls assigning the effects to TSPO.

    Evidence NBD-cholesterol imaging, cholesterol efflux assays, and pharmacological specificity controls (diazepam vs clonazepam) in astrocytes and fibroblasts

    PMID:17631921

    Open questions at the time
    • Pharmacology-only; no genetic confirmation
    • Single lab
  7. 2014 High

    Refuted the essential cholesterol-transport/steroidogenesis model by showing global Tspo knockout mice are viable with normal steroids, while revealing reduced microglial ATP—redirecting the field toward bioenergetics.

    Evidence Global Tspo knockout mouse with PET imaging, cholesterol/pregnenolone/protoporphyrin assays, and microglial ATP measurement

    PMID:25406832

    Open questions at the time
    • Compensatory adaptation in knockout not fully resolved
    • Mechanism linking TSPO to ATP not defined here
  8. 2014 High

    Defined the ligand-dependent conformational behaviour of TSPO, showing a rigid five-helix bundle when PK11195-bound versus dynamic exchange and local unfolding when unbound.

    Evidence Solution-state NMR structure of mouse TSPO with PK11195 and conformational dynamics analysis

    PMID:26394723 PMID:26551694

    Open questions at the time
    • Functional consequence of conformational dynamics in vivo unclear
    • Endogenous ligand state not captured
  9. 2015 High

    Provided atomic-resolution architecture of TSPO, defining the dimer, an endogenous porphyrin-binding site, and the structural impact of the human Ala147Thr polymorphism on cholesterol binding.

    Evidence X-ray crystallography of Rhodobacter TSPO in lipidic cubic phase with mutagenesis mimicking the human polymorphism

    PMID:25635101

    Open questions at the time
    • Bacterial ortholog; human-specific features inferred via mutagenesis
    • Cholesterol-transport function not demonstrated structurally
  10. 2016 High

    Established a direct metabolic function: TSPO loss shifts mitochondrial substrate use from glucose to fatty acids with elevated FAO and ROS, defining TSPO as a bioenergetic regulator.

    Evidence CRISPR/Cas9 knockout in MA-10 cells with Seahorse flux analysis, gene profiling, and corroboration in Tspo-/- mouse adrenal

    PMID:26741196

    Open questions at the time
    • Molecular mechanism coupling TSPO to substrate choice unknown
    • Direct lipid-handling activity not shown
  11. 2017 Medium

    Gain-of-function showed de novo TSPO expression upregulates ETC genes, raises ATP, and increases proliferation/motility, reinforcing a bioenergetic and growth-promoting role.

    Evidence Stable TSPO transfection into TSPO-low Jurkat cells with RT-qPCR, patch-clamp, ATP and proliferation/motility assays, plus PK11195 inhibition

    PMID:28103132

    Open questions at the time
    • Single cell system
    • Mechanism connecting TSPO to ETC gene transcription unresolved
  12. 2019 Medium

    Connected TSPO to organismal energy balance by showing tanycytic TSPO loss triggers AMPK-dependent lipophagy, reducing food intake and raising energy expenditure.

    Evidence Tanycyte-specific Rax-Cre knockout with ICV PK11195, metabolic cage studies, and lipophagy/AMPK pathway analysis

    PMID:31469345

    Open questions at the time
    • Direct molecular target of TSPO in lipophagy not identified
    • Single lab
  13. 2020 Medium

    Showed TSPO controls microglial activation through mitochondrial metabolism, with deficiency suppressing OXPHOS, glycolysis, membrane potential, and ATP.

    Evidence Knockout-derived primary microglia and siRNA knockdown with LPS/IL-4 activation and Seahorse metabolic analysis

    PMID:32695005

    Open questions at the time
    • Mechanism coupling TSPO to metabolic flux unresolved
    • Single lab
  14. 2020 Medium

    Identified neuronal activity as a driver of TSPO expression, refining interpretation of TSPO as a glial-activation imaging marker.

    Evidence Single-cell RNA-seq with DREADD chemogenetics, novel environment, and amphetamine stimulation plus confocal microscopy

    PMID:32398717

    Open questions at the time
    • Functional consequence of neuronal TSPO induction unknown
    • Single lab
  15. 2020 Medium

    Extended TSPO loss-of-function phenotypes to reproduction and lipid homeostasis, with delayed embryonic development and reduced testosterone alongside compensatory cholesterol-transport gene upregulation.

    Evidence Amhr2-Cre Tspo knockout with embryo morphology, testosterone ELISA, lipid analysis, and RNA-seq

    PMID:32099945

    Open questions at the time
    • Testosterone reduction contrasts with normal steroids in other knockouts
    • Compensatory mechanisms not mechanistically dissected
  16. 2020 High

    Placed TSPO upstream of NOX1-dependent neurotoxic ROS in retinal phagocytes, defining a controllable node in microglial reactivity and neovascular pathology.

    Evidence Cx3cr1-CreERT2 conditional knockout, XBD173 ligand treatment, and genetic epistasis with NADPH oxidase-deficient mice in a laser-induced CNV model

    PMID:32483169

    Open questions at the time
    • Biochemical link between TSPO and NOX1 not resolved
    • Generalizability beyond retina untested
  17. 2021 Medium

    Demonstrated TSPO is required for microglial phagocytic clearance of amyloid-β, with deficiency worsening plaque burden and inflammation in APP/PS1 mice.

    Evidence TSPO knockout in APP/PS1 background with primary microglial phagocytosis assays, cytokine ELISA, and plaque quantification

    PMID:34340010

    Open questions at the time
    • Mechanistic link from TSPO metabolism to phagocytosis not defined
    • Single lab
  18. 2021 Medium

    Revealed a role in retinal lipid homeostasis, with TSPO deletion elevating cholesterol/lipids, perturbing efflux, and inducing inflammation.

    Evidence Tspo knockout mouse retina with histology, biochemical lipid assays, gene profiling, and cytokine measurement

    PMID:34831289

    Open questions at the time
    • Direct lipid-transport activity not demonstrated
    • Cell-type contribution within retina unresolved
  19. 2022 High

    Showed diazepam-induced cognitive and spine deficits act through TSPO rather than GABAA receptors by enhancing microglial phagocytosis of synaptic material, reframing benzodiazepine neurotoxicity.

    Evidence TSPO-specific genetic manipulation, two-photon spine imaging, microglial phagocytosis assays, and PET in mice

    PMID:35228700

    Open questions at the time
    • Signaling cascade from TSPO ligand binding to phagocytosis unresolved
    • Endogenous ligand for this pathway unknown
  20. 2023 Medium

    Defined a physical TSPO–p62/SQSTM1 interaction that blocks autophagy and activates Nrf2 antioxidant and PD-L1 immune-evasion programs in tumor cells.

    Evidence Co-immunoprecipitation with gain/loss-of-function, autophagy assays, and Nrf2/KEAP1/p62 pathway analysis in HCC models

    PMID:36994647

    Open questions at the time
    • Co-IP without reciprocal structural validation of the interface
    • Interaction generality beyond HCC untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular activity that couples TSPO's structural dynamics and ligand binding to its downstream control of mitochondrial substrate use, ROS, autophagy, and phagocytosis, and the identity of its physiological endogenous ligand, remain undefined.
  • No defined enzymatic or transport activity for TSPO
  • Endogenous ligand mediating in vivo functions unidentified
  • Mechanistic chain from TSPO to bioenergetic/phagocytic outputs not reconstituted

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Crystal structures of TSPO from Rhodobacter sphaeroides at 1.8, 2.4, and 2.5 Å resolution (lipidic cubic phase) revealed a tightly interacting dimer, the binding site of an endogenous porphyrin ligand, and conformational effects of the human Ala147→Thr147 polymorphism on cholesterol binding. X-ray crystallography (lipidic cubic phase), site-directed mutagenesis to mimic human polymorphism Science High 25635101
2014 NMR structure of mouse TSPO in complex with PK11195 showed a rigid five-helix bundle when bound to the ligand; in the absence of PK11195, TSPO exchanges between multiple conformations with extensive motions on pico- to microsecond timescales and local unfolding near the ligand-binding site. NMR spectroscopy (solution-state), ligand binding/unbinding studies Science / Chemistry (Weinheim) High 26394723 26551694
2016 CRISPR/Cas9 knockout of TSPO in steroidogenic MA-10 Leydig cells caused a shift in mitochondrial substrate utilisation from glucose to fatty acids, with significantly higher fatty acid oxidation (FAO) and increased reactive oxygen species production, but no change in oxygen consumption rate, membrane potential, or proton leak; consistent upregulation of FAO genes was found in adrenal glands of global Tspo−/− mice. CRISPR/Cas9 knockout, Seahorse metabolic flux analysis, gene expression profiling, global TSPO knockout mouse model Endocrinology High 26741196
2014 Global C57BL/6 Tspo knockout mice are viable with normal growth, lifespan, cholesterol transport, blood pregnenolone concentration, protoporphyrin IX metabolism, fertility, and behaviour, directly challenging the model that TSPO is essential for cholesterol transport and steroidogenesis. However, microglia from TSPO knockouts produced significantly less ATP, indicating reduced metabolic activity. Global gene knockout mouse model, PET imaging with PK11195/CLINDE/PBR111, biochemical assays (cholesterol, pregnenolone, protoporphyrin IX), ATP measurement in isolated microglia Nature Communications High 25406832
2003 TSPO (PBR) interacts with PAP7, a protein that also binds the PKA regulatory subunit RIα; PAP7 is localized to Golgi and mitochondria. Inhibition of PAP7 expression reduced hormone-induced cholesterol transport into mitochondria and decreased steroid formation, placing PAP7 as an AKAP linking cAMP/PKA signalling to TSPO-mediated cholesterol transport. Protein interaction identification (phage display, co-immunoprecipitation), antisense oligonucleotide knockdown, steroid production assay Journal of Steroid Biochemistry and Molecular Biology Medium 12943713
2002 Antisense knockdown of TSPO (PBR) in MA-10 Leydig cells reduced PBR protein levels and inhibited hormone-stimulated steroid formation; a 7-mer competitive PBR peptide antagonist identified by phage display also inhibited benzodiazepine- and hormone-stimulated steroid production when transduced into Leydig cells, supporting the requirement for endogenous PBR agonist–receptor interaction in steroidogenesis. Antisense oligonucleotide knockdown, phage display peptide antagonist, steroid production assay Endocrine Research Medium 12530641
1992 Immunocytochemistry and confocal microscopy with 3D reconstruction in mouse adrenal cortex demonstrated that a subset of PBR/TSPO localises to the plasma membrane in zona fasciculata cells, in addition to the mitochondrial pool, suggesting functions not restricted to mitochondria. Anti-peptide immunocytochemistry, biotin-streptavidin peroxidase staining, confocal microscopy with 3D reconstruction Molecular and Cellular Endocrinology Medium 1332905
2020 TSPO deficiency (knockout mice and siRNA knockdown cell line) significantly inhibited microglial activation induced by LPS or IL-4, decreased mitochondrial membrane potential and ATP production, and suppressed both mitochondrial OXPHOS and glycolysis, demonstrating that TSPO regulates microglial activation through control of mitochondrial metabolism. TSPO knockout mouse-derived primary microglia, siRNA knockdown cell line, LPS/IL-4 activation assays, Seahorse metabolic analysis, mitochondrial membrane potential measurement, ATP assay Frontiers in Pharmacology Medium 32695005
2020 Conditional deletion of TSPO in retinal microglia (Cx3cr1-CreERT2:TSPOfl/fl) or treatment with the TSPO ligand XBD173 prevented microglial/phagocyte reactivity and subsequent neoangiogenesis in the laser-induced neovascular AMD model. Using NADPH oxidase-deficient mice, TSPO was identified as a key regulator of NOX1-dependent neurotoxic ROS production in the retina. Conditional knockout mouse (Cx3cr1-CreERT2:TSPOfl/fl), pharmacological ligand treatment (XBD173), NADPH oxidase-deficient mouse strains (genetic epistasis), laser-induced choroidal neovascularisation model Nature Communications High 32483169
2019 Tanycyte-specific deletion of TSPO (Rax-Cre) in the hypothalamus and intracerebroventricular administration of PK11195 reduced food intake and elevated energy expenditure in high-fat diet conditions; ablation of tanycytic TSPO elicited AMPK-dependent lipophagy, breaking down lipid droplets to free fatty acids and elevating ATP, linking TSPO to hypothalamic lipid sensing and energy balance via autophagy regulation. Tanycyte-specific conditional knockout (Rax-Cre), intracerebroventricular ligand injection, metabolic cage studies, lipophagy/autophagy assays, AMPK pathway analysis Autophagy Medium 31469345
2022 Diazepam impaired structural plasticity of dendritic spines and caused cognitive impairment in mice via TSPO (not GABAA receptors), altering microglial morphology and enhancing microglial phagocytosis of synaptic material (spine engulfment); this was demonstrated using TSPO-specific genetic approaches. In vivo mouse model, TSPO-specific genetic manipulation (knockouts/ligands), two-photon microscopy of spine dynamics, microglial phagocytosis assays, PET imaging Nature Neuroscience High 35228700
2023 TSPO directly interacts with p62/SQSTM1 in hepatocellular carcinoma cells, interfering with autophagy and causing p62 accumulation; accumulated p62 competes with KEAP1, preventing KEAP1-mediated proteasomal degradation of Nrf2, thereby activating Nrf2-dependent antioxidant defence to inhibit ferroptosis and upregulating PD-L1 expression to promote immune evasion. Co-immunoprecipitation (TSPO–p62 interaction), gain- and loss-of-function experiments, autophagy assays, Nrf2/KEAP1/p62 pathway analysis, PD-L1 expression measurement, in vitro and in vivo tumour models Advanced Science Medium 36994647
2017 Stable transfection of TSPO into TSPO-low Jurkat cells (de novo expression) increased transcription of mitochondrial electron transport chain genes, elevated ATP production, decreased rectified K+ channel currents, and increased cell proliferation and motility; these functional changes were inhibited by the TSPO ligand PK11195. Stable TSPO transfection into TSPO-deficient cells, RT-qPCR, radioligand binding, immunocytochemistry, patch-clamp electrophysiology, ATP assay, proliferation/motility assays Cell Cycle Medium 28103132
2021 Deletion of TSPO in mouse retina caused elevated levels of cholesterol, triglycerides, and phospholipids with perturbed cholesterol efflux in RPE cells, downregulation of cholesterol-associated genes (Nr1h3, Abca1, Abcg1, Cyp27a1, Cyp46a1), increased pro-inflammatory cytokines, and microglial activation, demonstrating a role for TSPO in retinal cholesterol homeostasis. Tspo knockout mouse retina, histology/immunohistochemistry, biochemical lipid assays, gene expression profiling, cytokine measurement Cells Medium 34831289
2021 TSPO-deficient microglia (in APP/PS1 background) showed a significant decrease in phagocytic capacity for Aβ peptides and latex beads, and generated more pro-inflammatory cytokines (TNF-α, IL-1β) in response to Aβ; APP/PS1 mice lacking TSPO had higher levels of Aβ1-40, Aβ1-42 and more amyloid plaques, indicating that TSPO is required for normal microglial phagocytic clearance of amyloid. TSPO knockout in APP/PS1 mouse model, primary microglial culture with phagocytosis assays (Aβ and latex beads), ELISA for cytokines and Aβ levels, amyloid plaque quantification Neurobiology of Aging Medium 34340010
2012 TSPO ligands (PK11195, Ro5-4864) induced redistribution of intracellular cholesterol into lipid droplets, blocked cholesterol esterification, increased cholesterol efflux, caused mitochondrial shrinkage and depolarisation, and depleted acidic vesicles in astrocytes and fibroblasts; these effects were reproduced by diazepam but not by clonazepam (GABAA-selective), linking the effects specifically to TSPO binding. Fluorescent cholesterol analogue (NBD-cholesterol) imaging, [3H]cholesterol efflux assay, MTT assay, immunocytochemistry, pharmacological specificity controls Neuropharmacology Medium 17631921
1993 TSPO (mDRC/PBR) ligands of the 2-arylindole-3-acetamide class stimulated pregnenolone formation from mitochondria of C6-2B glioma cells with an EC50 of ~3 nM, directly linking TSPO pharmacology to mitochondrial neurosteroid biosynthesis. In vitro steroid synthesis assay (C6-2B glioma cell mitochondria), radioligand displacement ([3H]4'-chlorodiazepam binding), structure-activity relationship studies Journal of Medicinal Chemistry Medium 8411007
2004 RNAi knockdown of TSPO (PBR) in human fibroblasts and fibrosarcoma cells did not affect cell proliferation and did not influence the anti-proliferative effect of PK11195 or Ro5-4864, demonstrating that these ligands inhibit proliferation through PBR-independent mechanisms in mesenchymal cells. RNAi knockdown, cell proliferation assay, cell cycle analysis (G0/G1 arrest), ERK/c-Jun activation assays Biochemical Pharmacology Medium 15130769
2020 Chemogenetic (DREADDs), physiological (novel environment), and pharmacological (amphetamine) stimulation of neuronal activity consistently increased TSPO gene and protein levels in neurons but not in microglia or astrocytes in the adult mouse brain, as confirmed by single-cell RNA sequencing and confocal microscopy. Single-cell RNA sequencing, DREADDs chemogenetics, pharmacological stimulation, confocal laser scanning microscopy, TSPO mRNA/protein quantification Molecular Psychiatry Medium 32398717
2020 Amhr2-Cre-mediated global Tspo knockout mice showed delayed preimplantation embryonic development (66.7% of blastocysts at E3.5–4.5 showed delayed morphology), disturbances in neutral lipid homeostasis, reduced intratesticular and circulating testosterone, and transcriptome changes in adrenal glands and lungs including upregulation of cholesterol-binding and transfer proteins as compensatory responses. Conditional/global Tspo knockout (Amhr2-Cre), embryo morphology analysis, testosterone/corticosterone ELISA, lipid analysis, RNA-sequencing Journal of the Endocrine Society Medium 32099945
2019 Diazepam activated TSPO (PBR) in melanocytes, increasing intracellular cAMP and PKA-mediated CREB phosphorylation, which in turn upregulated tyrosinase, MITF, Rab27a, Myosin Va, Rab17, and Cdc42, enhancing melanin synthesis, melanocyte dendricity, and melanosome transport/capture at dendrite tips. Masson-Fontana silver staining, scanning electron microscopy, immunocytochemistry, western blot, pharmacological PBR activation International Journal of Biochemistry & Cell Biology Low 31561018

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Small mobilizable multi-purpose cloning vectors derived from the Escherichia coli plasmids pK18 and pK19: selection of defined deletions in the chromosome of Corynebacterium glutamicum. Gene 2370 8045426
2010 Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorders. Nature reviews. Drug discovery 780 21119734
2008 Translocator protein 18 kDa (TSPO): molecular sensor of brain injury and repair. Pharmacology & therapeutics 425 18374421
2012 Reactive astrocytes overexpress TSPO and are detected by TSPO positron emission tomography imaging. The Journal of neuroscience : the official journal of the Society for Neuroscience 302 22875916
2010 Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Molecular and cellular endocrinology 239 20600583
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 218 17692008
2014 Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nature communications 208 25406832
2015 The methodology of TSPO imaging with positron emission tomography. Biochemical Society transactions 197 26551697
2008 VDAC activation by the 18 kDa translocator protein (TSPO), implications for apoptosis. Journal of bioenergetics and biomembranes 162 18670869
2009 Evaluation of the PBR/TSPO radioligand [(18)F]DPA-714 in a rat model of focal cerebral ischemia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 150 19794397
2018 Emerging PET Radiotracers and Targets for Imaging of Neuroinflammation in Neurodegenerative Diseases: Outlook Beyond TSPO. Molecular imaging 148 30203712
2015 Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases? Journal of nuclear medicine : official publication, Society of Nuclear Medicine 147 26697963
2021 Cellular sources of TSPO expression in healthy and diseased brain. European journal of nuclear medicine and molecular imaging 145 33433698
2009 Translocator protein (18 kDa) TSPO: an emerging therapeutic target in neurotrauma. Experimental neurology 144 19409385
2020 Recent developments on PET radiotracers for TSPO and their applications in neuroimaging. Acta pharmaceutica Sinica. B 142 33643818
2017 Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases. International journal of molecular sciences 140 28387722
2015 Protein structure. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science (New York, N.Y.) 135 25635101
2023 Mitochondrial TSPO Promotes Hepatocellular Carcinoma Progression through Ferroptosis Inhibition and Immune Evasion. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 116 36994647
2020 The Translocator Protein (TSPO) in Mitochondrial Bioenergetics and Immune Processes. Cells 115 32102369
2003 Expression of peripheral benzodiazepine receptor (PBR) in human tumors: relationship to breast, colorectal, and prostate tumor progression. Journal of receptor and signal transduction research 113 14626449
2015 The changing landscape in translocator protein (TSPO) function. Trends in endocrinology and metabolism: TEM 101 25801473
2020 Neuronal activity increases translocator protein (TSPO) levels. Molecular psychiatry 100 32398717
2018 PET Imaging of Microglial Activation-Beyond Targeting TSPO. Molecules (Basel, Switzerland) 99 29518005
1993 Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands. Journal of medicinal chemistry 96 8411007
2016 Translocator Protein 18 kDa (TSPO): An Old Protein with New Functions? Biochemistry 95 27074410
2019 VDAC1 and the TSPO: Expression, Interactions, and Associated Functions in Health and Disease States. International journal of molecular sciences 93 31288390
2021 Imaging neuroinflammation with TSPO: A new perspective on the cellular sources and subcellular localization. Pharmacology & therapeutics 87 34848203
2016 Translocator Protein (TSPO) Affects Mitochondrial Fatty Acid Oxidation in Steroidogenic Cells. Endocrinology 86 26741196
2013 The translocator protein (TSPO): a novel target for cancer chemotherapy. The international journal of biochemistry & cell biology 77 23518318
2012 The role of 18 kDa mitochondrial translocator protein (TSPO) in programmed cell death, and effects of steroids on TSPO expression. Current molecular medicine 77 22348610
2018 Increased Expression of Translocator Protein (TSPO) Marks Pro-inflammatory Microglia but Does Not Predict Neurodegeneration. Molecular imaging and biology 76 28695372
2018 TSPO: An Evolutionarily Conserved Protein with Elusive Functions. International journal of molecular sciences 73 29875327
2018 TSPO upregulation in bipolar disorder and concomitant downregulation of mitophagic proteins and NLRP3 inflammasome activation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 72 30575805
1992 Cell surface localization of the peripheral-type benzodiazepine receptor (PBR) in adrenal cortex. Molecular and cellular endocrinology 72 1332905
2022 Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO). Nature neuroscience 69 35228700
2003 PAP7, a PBR/PKA-RIalpha-associated protein: a new element in the relay of the hormonal induction of steroidogenesis. The Journal of steroid biochemistry and molecular biology 68 12943713
2015 Mitochondrial translocator protein (TSPO): From physiology to cardioprotection. Biochemical pharmacology 67 26688086
2012 The 18 kDa translocator protein (TSPO): a new perspective in mitochondrial biology. Current molecular medicine 67 22364127
2020 Translocator protein (TSPO): the new story of the old protein in neuroinflammation. BMB reports 65 31818362
2020 Translocator Protein 18 kDa (TSPO) Deficiency Inhibits Microglial Activation and Impairs Mitochondrial Function. Frontiers in pharmacology 65 32695005
2016 TSPO: kaleidoscopic 18-kDa amid biochemical pharmacology, control and targeting of mitochondria. The Biochemical journal 65 26733718
2020 In Vivo TSPO Signal and Neuroinflammation in Alzheimer's Disease. Cells 64 32839410
2004 Peripheral-type benzodiazepine receptor (PBR) and PBR drug ligands in fibroblast and fibrosarcoma cell proliferation: role of ERK, c-Jun and ligand-activated PBR-independent pathways. Biochemical pharmacology 64 15130769
2020 The TSPO-NOX1 axis controls phagocyte-triggered pathological angiogenesis in the eye. Nature communications 63 32483169
2017 Functional gains in energy and cell metabolism after TSPO gene insertion. Cell cycle (Georgetown, Tex.) 61 28103132
2017 A TSPO ligand attenuates brain injury after intracerebral hemorrhage. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 61 28416580
2015 Minireview: translocator protein (TSPO) and steroidogenesis: a reappraisal. Molecular endocrinology (Baltimore, Md.) 61 25730708
2016 TSPO Finds NOX2 in Microglia for Redox Homeostasis. Trends in pharmacological sciences 58 27113160
2019 Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance. Autophagy 57 31469345
2002 PBR, StAR, and PKA: partners in cholesterol transport in steroidogenic cells. Endocrine research 56 12530641
2015 TSPO is a REDOX regulator of cell mitophagy. Biochemical Society transactions 55 26551691
2016 TSPO expression in brain tumours: is TSPO a target for brain tumour imaging? Clinical and translational imaging 54 27077069
2021 TSPO imaging in animal models of brain diseases. European journal of nuclear medicine and molecular imaging 53 34245328
2020 Astrocytic TSPO Upregulation Appears Before Microglial TSPO in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 52 32804124
2015 Enigmatic Translocator protein (TSPO) and cellular stress regulation. Trends in biochemical sciences 51 26228316
2022 Neuroinflammation PET imaging of the translocator protein (TSPO) in Alzheimer's disease: An update. The European journal of neuroscience 50 35083791
2020 The Role of Translocator Protein TSPO in Hallmarks of Glioblastoma. Cancers 50 33066460
2012 Translocator protein (18 kDa) (TSPO) as a therapeutic target for anxiety and neurologic disorders. European archives of psychiatry and clinical neuroscience 48 22923187
2020 An update into the medicinal chemistry of translocator protein (TSPO) ligands. European journal of medicinal chemistry 46 33081988
2015 Imaging neuroinflammation in multiple sclerosis using TSPO-PET. Clinical and translational imaging 46 27331049
2019 TSPO Ligands Boost Mitochondrial Function and Pregnenolone Synthesis. Journal of Alzheimer's disease : JAD 44 31256132
2012 Translocator protein (TSPO) and neurosteroids: implications in psychiatric disorders. Current molecular medicine 44 22348611
2021 Supervised clustering for TSPO PET imaging. European journal of nuclear medicine and molecular imaging 41 33779770
2014 Translocator protein (TSPO) role in aging and Alzheimer's disease. Current aging science 41 25495567
2017 TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases? Contrast media & molecular imaging 40 29114179
2008 Peripheral benzodiazepine receptor (PBR) new insight in cell proliferation and cell differentiation review. Current clinical pharmacology 40 18690876
2011 Structural requirements to obtain highly potent and selective 18 kDa Translocator Protein (TSPO) Ligands. Current topics in medicinal chemistry 39 21291396
2005 Peripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression. Biochemical pharmacology 39 15710359
2019 Prospects and challenges of imaging neuroinflammation beyond TSPO in Alzheimer's disease. European journal of nuclear medicine and molecular imaging 38 31396666
2017 Regulation of Mitochondrial, Cellular, and Organismal Functions by TSPO. Advances in pharmacology (San Diego, Calif.) 38 29413517
2016 Tetrapyrroles as Endogenous TSPO Ligands in Eukaryotes and Prokaryotes: Comparisons with Synthetic Ligands. International journal of molecular sciences 38 27271616
2016 Current status and future perspectives: TSPO in steroid neuroendocrinology. The Journal of endocrinology 35 27422254
2020 Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells. International journal of molecular sciences 34 31963507
2007 Intracellular cholesterol changes induced by translocator protein (18 kDa) TSPO/PBR ligands. Neuropharmacology 32 17631921
2016 Translocator protein (TSPO) ligands for the diagnosis or treatment of neurodegenerative diseases: a patent review (2010-2015; part 1). Expert opinion on therapeutic patents 31 27607364
2002 Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells. Cancer genetics and cytogenetics 31 12547158
2021 Imaging of the glioma microenvironment by TSPO PET. European journal of nuclear medicine and molecular imaging 30 33721063
2021 Applicability, potential and limitations of TSPO PET imaging as a clinical immunopsychiatry biomarker. European journal of nuclear medicine and molecular imaging 29 33735406
2012 Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 29 22956240
2022 Neurosteroids and translocator protein 18 kDa (TSPO) in depression: implications for synaptic plasticity, cognition, and treatment options. European archives of psychiatry and clinical neuroscience 28 36574032
2015 Structure of the mammalian TSPO/PBR protein. Biochemical Society transactions 28 26551694
2019 Insight into the Structural Features of TSPO: Implications for Drug Development. Trends in pharmacological sciences 27 31864680
2024 PET imaging of neuroinflammation: any credible alternatives to TSPO yet? Molecular psychiatry 26 38997465
2015 Conformational Flexibility in the Transmembrane Protein TSPO. Chemistry (Weinheim an der Bergstrasse, Germany) 26 26394723
2010 TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT. ACS medicinal chemistry letters 25 24900292
2024 Emerging TSPO-PET Radiotracers for Imaging Neuroinflammation: A Critical Analysis. Seminars in nuclear medicine 24 39477764
2023 Designed bacteria based on natural pbr operons for detecting and detoxifying environmental lead: A mini-review. Ecotoxicology and environmental safety 24 37939554
2017 An Updated View of Translocator Protein (TSPO). International journal of molecular sciences 24 29211020
2016 Translocator protein (TSPO) ligands for the diagnosis or treatment of neurodegenerative diseases: a patent review (2010 - 2015; part 2). Expert opinion on therapeutic patents 24 27599163
2015 Targeting mitochondrial energy metabolism with TSPO ligands. Biochemical Society transactions 23 26551690
2021 TSPO protein binding partners in bacteria, animals, and plants. Journal of bioenergetics and biomembranes 22 34191248
2015 TSPO as a target for glioblastoma therapeutics. Biochemical Society transactions 22 26551689
2009 ABA, porphyrins and plant TSPO-related protein. Plant signaling & behavior 22 19838071
2021 TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis. Neurobiology of aging 21 34340010
2015 Evolving understanding of translocator protein 18 kDa (TSPO). Pharmacological research 21 25882248
2024 TSPO Radioligands for Neuroinflammation: An Overview. Molecules (Basel, Switzerland) 20 39275061
2022 18F-Radiolabeled Translocator Protein (TSPO) PET Tracers: Recent Development of TSPO Radioligands and Their Application to PET Study. Pharmaceutics 20 36432736
2021 Deletion of TSPO Causes Dysregulation of Cholesterol Metabolism in Mouse Retina. Cells 20 34831289
2020 Amhr2-Cre-Mediated Global Tspo Knockout. Journal of the Endocrine Society 20 32099945
2019 Diazepam enhances melanogenesis, melanocyte dendricity and melanosome transport via the PBR/cAMP/PKA pathway. The international journal of biochemistry & cell biology 20 31561018

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