Journal
TRENDS IN ENDOCRINOLOGY AND METABOLISM
Volume 26, Issue 7, Pages 349-356Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tem.2015.04.001
Keywords
neuroinflammation; neuroimaging; peripheral benzodiazepine receptor; heme metabolism; REV-ERB alpha; mitochondrial permeability transition pore; cholesterol
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Funding
- Deutsche Forschungsgemeinschaft [Collaborative Research Center 803]
- European Research Council [282008]
- Deutsche Forschungsgemeinschaft
- European Framework Programme (FP6)
- Medical Research Council of the UK
- Australian Research Council
- Australian Nuclear Science and Technology Organisation
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Research spanning nearly four decades has assigned to the translocator protein (18 kDa) (TSPO) a critical role, among others, in the mitochondrial import of cholesterol, the subsequent steps of (neuro)steroid production, and systemic endocrine regulation, with implications for the pathophysiology of immune, inflammatory, neurodegenerative, and psychiatric as well as neoplastic diseases. Recent knockout studies in mice unexpectedly report normal or latent phenotypes, raising doubts about the protein's role in steroidogenesis and other previously postulated functions and challenging the validity of earlier data on the selectivity of TSPO-binding drugs. Here we provide a synthesis of the current debate from a structural and molecular biology perspective, discuss the limits of inference in loss-of-function (gene knockout) studies, and suggest new functions of TSPO.
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