The Translocator Protein (18 kDa)
The translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), is a mitochondrial outer membrane protein that is highly conserved across species from bacteria to mammals. The TSPO is associated with crucial cellular functions: steroid hormone production, transport of cholesterol into the mitochondria, as well as energy metabolism and the regulation of inflammatory immune responses.
History and role of TSPO
Nearly 3 billion years ago, in the early days of life on Earth, when oxygen levels in the atmosphere dramatically rose, a family of small proteins - translocator proteins - evolved in bacteria, and has been conserved ever since throughout the plant and animal kingdoms.
In plants, proteins of the TSPO family play a role in photosynthesis, while in humans they regulate the production of sex and stress hormones. Unsurprisingly, it has long been thought that a protein that has changed little for billions of years must be essential for life.
Researchers at ANSTO have now disproved this long-held view about the TSPO and are starting to re-write our understanding on how hormones are produced and regulated.
The future of research and development into TSPO
TSPO expression levels have been shown to be highly increased in a variety of disease states and to correlate with the severity of illness and rate of illness progression. Over the last fifteen years, research into the TSPO as a widely applicable diagnostic and therapeutic target has intensified significantly. As of 2014, there have been well over 30 clinical trials involving the measurements or the therapeutic targeting of TSPO in disease conditions ranging from inflammation to neurodegeneration and behavioural illnesses.
The use of the TSPO knockout mouse model will allow for the molecular function of TSPO in disease to be understood in greater detail, and be tested in vivo under realistic and controlled conditions. This is a crucial step towards the rational and accelerated development of next generation therapeutics targeting TSPO related functions in disease.