Translocator Protein (TSPO) and Neurosteroids: Implications in Psychiatric Disorders

E.      Da Pozzo; B.      Costa; C.      Martini

Abstract

The translocator protein (TSPO) is a five transmembrane domain protein localised primarily in the outer mitochondrial membrane of steroid-synthesizing tissues, including the brain. The TSPO mediates the rate-limiting step of steroidogenesis, consisting of the translocation of the substrate cholesterol from the outer to the inner mitochondrial membrane. In the recent years TSPO function has received attention in several psychiatric disorders since these diseases have been associated with unbalanced steroid levels. Accordingly, an alteration in the levels of TSPO has been found in various psychiatric disorders, including social phobia, post-traumatic stress disorder, adult separation anxiety and schizophrenia. The discovery that TSPO drug ligands are able to stimulate neurosteroid production in the brain, independently of peripheral endocrine sources, and restore neurosteroid-mediated neurotransmission, has made the TSPO an attractive drug target for treating a number of psychiatric disorders. In anxiety TSPO drug ligands have shown in vivo efficacy in pharmacologically induced anxiety models in both animals and humans.

The focus of this review is to illustrate the currently available literature regarding the role of TSPO in psychiatric disorders.

Keywords: Anxiety disorders, mood disorders, neurosteroids, neurotransmission, psychotic disorders, stress disorders, translocator protein, TSPO ligands