title: The 18 kDa translocator protein, microglia and neuroinflammation.
abstract: The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is expressed in the injured brain. It has become known as an imaging marker of "neuroinflammation" indicating active disease, and is best interpreted as a nondiagnostic biomarker and disease staging tool that refers to histopathology rather than disease etiology. The therapeutic potential of TSPO as a drug target is mostly based on the understanding that it is an outer mitochondrial membrane protein required for the translocation of cholesterol, which thus regulates the rate of steroid synthesis. This pivotal role together with the evolutionary conservation of TSPO has underpinned the belief that any loss or mutation of TSPO should be associated with significant physiological deficits or be outright incompatible with life. However, against prediction, full Tspo knockout mice are viable and across their lifespan do not show the phenotype expected if cholesterol transport and steroid synthesis were significantly impaired. Thus, the "translocation" function of TSPO remains to be better substantiated. Here, we discuss the literature before and after the introduction of the new nomenclature for TSPO and review some of the newer findings. In light of the controversy surrounding the function of TSPO, we emphasize the continued importance of identifying compounds with confirmed selectivity and suggest that TSPO expression is analyzed within specific disease contexts rather than merely equated with the reified concept of "neuroinflammation."
authors.affiliation: Life Sciences, Australian Nuclear Science and Technology Organisation, NSW, Australia; Brain & Mind Research Institute, The University of Sydney, NSW, Australia; Discipline of Medical Imaging & Radiation Sciences, Faculty of Health Sciences, The University of Sydney, NSW, Australia.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Liu
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Middleton
authors.forename: Claire R
authors.initials: CR
authors.lastname: Hatty
authors.forename: Winnie Wai-Ying
authors.initials: WW
authors.lastname: Kam
authors.forename: Ronald
authors.initials: R
authors.lastname: Chan
authors.forename: Tien
authors.initials: T
authors.lastname: Pham
authors.forename: Meredith
authors.initials: M
authors.lastname: Harrison-Brown
authors.forename: Eoin
authors.initials: E
authors.lastname: Dodson
authors.forename: Kelly
authors.initials: K
authors.lastname: Veale
authors.forename: Richard B
authors.initials: RB
authors.lastname: Banati
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000502:physiology; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*
chemical_list: D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: PBR111; PET; PK11195; TSPO; microglia; neuroinflammation