18-kDa translocator protein association complexes in the brain: From structure to function

The outer mitochondrial membrane 18-kDa translocator protein (TSPO) is highly conserved in organisms of different species and ubiquitously expressed throughout tissues, including the nervous system. In the healthy adult brain, TSPO expression levels are low and promptly modulated under different pathological conditions, such as cancer, inflammatory states, and neurological and psychiatric disorders. Not surprisingly, several endogenous and synthetic molecules capable of binding TSPO have been proposed as drugs or diagnostic tools for brain diseases. The most studied biochemical function of TSPO is cholesterol translocation into mitochondria, which in turn affects the synthesis of steroids in the periphery and neurosteroids in the brain. In the last 30 years, roles for TSPO have also been suggested in other cellular processes, such as heme synthesis, apoptosis, autophagy, calcium signalling and reactive oxygen species production. Herein, we provide an overview of TSPO associations with different proteins, focusing particular attention on their related functions. Furthermore, recent TSPO-targeted therapeutic interventions are explored and discussed as prospect for innovative treatments in mental and brain diseases.