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Eur Arch Psychiatry Clin Neurosci. 2012 Nov;262 Suppl 2:S107-12. doi: 10.1007/s00406-012-0352-5. Epub 2012 Aug 26.

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

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1
Department of Psychiatry and Psychotherapy, University Regensburg, Universitätsstraße 84, 93053 Regensburg, Germany. Caroline.Nothdurfter@medbo.de

Abstract

The translocator protein (18 kD) (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 GABA(A) 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 GABA(A) 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.

PMID:
22923187
DOI:
10.1007/s00406-012-0352-5
[Indexed for MEDLINE]
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