Editorial Current Molecular Medicine, 2012, Vol. 12, No. 4 355 EDITORIAL The Physiology and Pharmacology of the Mitochondrial 18 kDa Translocator Protein (TSPO): An Emerging Molecular Target for Diagnosis and Therapy

The need for a focused issue covering the physiology and pharmacology of the Translocator Protein (TSPO) was in demand for quite some time; this to both summarize the current knowledge on this fascinating molecule and to boost interest in experimental biologists, pharmacologists and clinicians. The leading and most representative experts on the subject have therefore contributed with enthusiasm to its realization thus generating a memorable editorial occasion that besides collecting the exploited features of TSPO also shares original data to inspire future research angles of investigation. TSPO -formerly known as the Peripheral Benzodiazepine Receptor (PBR)- is an ubiquitous 18 kDa molecule on which the synthesis of steroids depends. Located on the outer mitochondrial membrane (OMM), it is critical for the modulation of mitochondrial pathophysiology by standing -and possibly interacting with- the ‘putative’ molecules composing the mitochondrial permeability transition pore. TSPO binds cholesterol with great affinity, and similarly the endozapines as well as synthetic ligands such as: a) the benzodiazepine 4'-chlorodiazepam Ro5-4864 and b) the isoquinoline carboxamide PK11195. Although the latter, as you will learn in this issue, affects mitochondrial biology independently from its most acknowledged target. TSPO associates with the inflammatory states of the Central Nervous System (CNS) and positively correlates with tumor progression and malignancy besides playing a part in the pathophysiology of the kidney in which it defines the response to ischemia and reperfusion. Physiological and pathological processes linked to this protein range therefore from metabolism to inflammation, and cell death, making TSPO a prime element in cellular and systemic homeostasis. Unsurprisingly, since envisaged as a logical target for novel diagnostics and therapeutics, the development of chemicals designed to bind and modulate TSPO has been quite substantial and hitherto essential to discover what is known of its physiology and pathology. This issue will provide therefore the reader with an organic overview of the relevant findings on TSPO, explaining the gene’s evolution, its involvement in organ pathology, and the diagnostic/therapeutic applications together with evidences on the functional role of its ligands. I therefore warmly recommend this selection of articles that, by pinpointing the past work, concomitantly inform on future avenues to improve the understanding of this pleiotropic molecule.

Michelangelo Campanella (Guest Editor) , University of , and University College London Consortium for Mitochondrial Research, Royal College Street, NW1 0TU, London, United Kingdom; European Brain Research Institute, Rita Levi-Montalcini Foundation, 00143 Rome, Italy Tel: 0044/02074681239, Ext: 5430; Fax: 0044/020 7468 5204; E-mail: [email protected]