期刊
TRENDS IN ENDOCRINOLOGY AND METABOLISM
卷 26, 期 7, 页码 349-356出版社
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tem.2015.04.001
关键词
neuroinflammation; neuroimaging; peripheral benzodiazepine receptor; heme metabolism; REV-ERB alpha; mitochondrial permeability transition pore; cholesterol
资金
- 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
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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