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  The 18-kDa Translocator Protein as a CNS Drug Target: Finding Our Way Through the Neuroinflammation Fog

Filiou, M. D., Banati, R. B., & Graeber, M. B. (2017). The 18-kDa Translocator Protein as a CNS Drug Target: Finding Our Way Through the Neuroinflammation Fog. CNS & NEUROLOGICAL DISORDERS, DRUG TARGETS, 16(9), 990-999. doi:10.2174/1871527316666171004125107.

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Datensatz-Permalink: http://hdl.handle.net/21.11116/0000-0001-844C-5 Versions-Permalink: http://hdl.handle.net/21.11116/0000-0001-844D-4
Genre: Zeitschriftenartikel

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 Urheber:
Filiou, Michaela D.1, Autor              
Banati, Richard B.2, Autor
Graeber, Manuel B.2, Autor
Affiliations:
1Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035294              
2external, ou_persistent22              

Inhalt

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Schlagwörter: PERIPHERAL BENZODIAZEPINE-RECEPTOR; POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; 18 KDA TSPO; ADULT SEPARATION ANXIETY; AMYOTROPHIC-LATERAL-SCLEROSIS; PERMEABILITY TRANSITION PORE; DIAZEPAM-BINDING INHIBITOR; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURYNeurosciences & Neurology; Pharmacology & Pharmacy; Astrocytes; microglia; mitochondria; neuroinflammation; neuropsychiatric disorders; PK11195; TSPO;
 Zusammenfassung: Background & Objective: The 18-kDa translocator protein (TSPO) is located in the outer mitochondrial membrane where it is thought to co-regulate steroidogenesis, cellular bioenergetics as well as several other cellular processes. Originally discovered as a binding site for diazepam outside the CNS, notably in steroidogenic tissue and mononuclear phagocytes, the TSPO's historical designation was peripheral benzodiazepine receptor. Much of the recent interest in TSPO is due to the observation that its regulation in the brain is associated with microglial activation. Importantly, this activation can be visualized in vivo by positron emission tomography (PET) using TSPO ligands. TSPO levels in normal brain tissue are close to current detection limits, being restricted to blood vessels and possibly areas of natural cell turnover. However, any progressive tissue damage is associated with a marked increase in TSPO expression, most prominently in activated microglia. Therefore, the inducible TSPO expression can serve as an exquisitely responsive sensor in a range of active brain pathologies, which are often conflated under the term 'neuroinflammation'. However, what occurs histologically in 'neuroinflammation' is different from classical brain tissue inflammation in the vast majority of cases. The resulting conceptual confusion poses potentially significant risks for patients who receive misguided anti-inflammatory treatment. It also obscures the fact that microglia may have other important roles, notably at synapses. 'Neuroinflammation' is at the current level of our understanding primarily the observation of dynamic tissue changes in the brain, the relevance of which for disease progression or brain plasticity phenomena is likely to be context dependent and remains to be worked out in detail. Here, we discuss the potential of TSPO as a therapeutic drug target for CNS disorders. Conclusion: In this review, we focus on psychiatric and neurodegenerative disorders, elaborate the role of TSPO and the effects of TSPO ligands on common disease phenotypes reviewing evidence from both animal models and patient cohorts and discuss future directions. As a modulator of pivotal cell processes, TSPO may serve as a drug target in well defined translational applications.

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Sprache(n): eng - Englisch
 Datum: 2017
 Publikationsstatus: Im Druck publiziert
 Seiten: 10
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Art des Abschluß: -

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Titel: CNS & NEUROLOGICAL DISORDERS, DRUG TARGETS
Genre der Quelle: Zeitschrift
 Urheber:
Affiliations:
Ort, Verlag, Ausgabe: BENTHAM SCIENCE PUBL
Seiten: - Band / Heft: 16 (9) Artikelnummer: - Start- / Endseite: 990 - 999 Identifikator: ISSN: 1871-5273