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Translocator protein (18 kDa) (TSPO) as a therapeutic target for anxiety and neurologic disorders

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Abstract

The translocator protein (18kD) (TSPO) plays a crucial role for the synthesis of neurosteroids by promoting the transport of cholesterol to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Neurosteroids are allosteric modulators of GABAA receptor function, which plays an important role in the pathophysiology of anxiety disorders. The TSPO ligand XBD173 enhances GABAergic neurotransmission by promoting neurosteroidogenesis without direct effects at the GABAA receptor. In humans, XBD173 shows potent antipanic efficacy without sedation and withdrawal after 7 days of treatment. XBD173 therefore appears to be a promising compound for rapid anxiolytic efficacy with a favorable side-effect profile. Furthermore, TSPO ligands show neuroprotective and antiinflammatory effects in experimental models of peripheral neuropathies and traumatic brain injury. These compounds might therefore also be valuable for the treatment of neurologic diseases with inflammation-related pathophysiology.

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Acknowledgments

This article is part of the supplement “Personalized Psychiatry and Psychotherapy”. This supplement was not sponsored by outside commercial interests. It was funded by the German Association for Psychiatry and Psychotherapy (DGPPN).

Conflict of interest

R. Rupprecht has been on Novartis advisory boards. The clinical study on XBD173 (46) has been sponsored by Novartis, Switzerland. C. Nothdurfter, T. C. Baghai and C. Schüle declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University Regensburg, Universitätsstraße 84, 93053, Regensburg, Germany

    Caroline Nothdurfter, Thomas C. Baghai & Rainer Rupprecht

  2. Max-Planck-Institute of Psychiatry, 80804, Munich, Germany

    Caroline Nothdurfter & Rainer Rupprecht

  3. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, 80336, Munich, Germany

    Cornelius Schüle

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  1. Caroline Nothdurfter
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  4. Rainer Rupprecht
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Correspondence to Caroline Nothdurfter.

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Nothdurfter, C., Baghai, T.C., Schüle, C. et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for anxiety and neurologic disorders. Eur Arch Psychiatry Clin Neurosci 262 (Suppl 2), 107–112 (2012). https://doi.org/10.1007/s00406-012-0352-5

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