Translocator protein and new targets for neuroinflammation

The mitochondrial translocator protein (18 kDa; TSPO) is involved in a wide array of physiological processes importantly including cholesterol transport, steroidogenesis and immunomodulation. In the central nervous system (CNS), TSPO expression regionally increases in glial cells upon brain insult with a differential pattern suggestive of cell-specific functions in inflammation and repair. These properties have made TSPO a valuable marker to assess the state, and progression of diverse neurological and psychiatric conditions, including traumatic brain injury, stroke, neurodegenerative diseases, anxiety, depression and schizophrenia. In the past years, an increasing number of radiolabeled TSPO ligands for the visualization and quantification of TSPO through positron emission tomography (PET), single-photon emission tomography (SPECT) and magnetic resonance imaging (MRI) have been developed in the pursuit of higher sensitivity and specificity for clinical applications. However, TSPO is not the only molecule holding great potential as an imaging marker of neuroinflammation; cell adhesion molecules, such as VCAM-1 and ICAM-1, the myeloperoxidase, matrix metalloproteinases, the cannabinoid receptor 2 (CB2), P2X7, cyclooxygenase 1 (COX-1), free radicals and leukocyte populations have also been subjects of study as targets to image inflammatory processes in the injured or diseased brain. In this review, we present the most relevant aspects of TSPO molecular features that fundament its imaging applications in the context of neuroinflammation, and comment on the development of imaging agents and strategies targeting TSPO as well as other molecules and cells implicated in inflammatory processes.