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Publication : Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases.

First Author  Nutma E Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  5247
PubMed ID  37640701 Mgi Jnum  J:340856
Mgi Id  MGI:7527941 Doi  10.1038/s41467-023-40937-z
Citation  Nutma E, et al. (2023) Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases. Nat Commun 14(1):5247
abstractText  Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation in vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases in activated microglia in mouse brain disease models but does not change in a non-human primate disease model or in common neurodegenerative and neuroinflammatory human diseases. We describe genetic divergence in the TSPO gene promoter, consistent with the hypothesis that the increase in TSPO expression in activated myeloid cells depends on the transcription factor AP1 and is unique to a subset of rodent species within the Muroidea superfamily. Finally, we identify LCP2 and TFEC as potential markers of microglial activation in humans. These data emphasise that TSPO expression in human myeloid cells is related to different phenomena than in mice, and that TSPO-PET signals in humans reflect the density of inflammatory cells rather than activation state.
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