2023-09-25 インペリアル・カレッジ・ロンドン(ICL)
◆これは、TSPOが活性化したミクログリア(脳内の特化した免疫細胞)のマーカーであると考えられていたが、ヒトではその信号が明確でないことを示唆しています。
◆この研究結果は臨床研究に大きな影響を及ぼし、新薬候補の評価などで広く使用されていたTSPOがその用途に適していない可能性があることを示唆しています。
<関連情報>
- https://www.imperial.ac.uk/news/247934/brain-imaging-tool-falls-short-human/
- https://www.nature.com/articles/s41467-023-40937-z
トランスロケータータンパク質はげっ歯類モデルにおける活性化ミクログリアのマーカーであるが、ヒトの神経変性疾患ではマーカーではない Translocator protein is a marker of activated microglia in rodent models but not human neurodegenerative diseases
Erik Nutma,Nurun Fancy,Maria Weinert,Stergios Tsartsalis,Manuel C. Marzin,Robert C. J. Muirhead,Irene Falk,Marjolein Breur,Joy de Bruin,David Hollaus,Robin Pieterman,Jasper Anink,David Story,Siddharthan Chandran,Jiabin Tang,Maria C. Trolese,Takashi Saito,Takaomi C. Saido,Katharine H. Wiltshire,Paula Beltran-Lobo,Alexandra Phillips,Jack Antel,Luke Healy,Marie-France Dorion,Dylan A. Galloway,Rochelle Y. Benoit,Quentin Amossé,Kelly Ceyzériat,Aurélien M. Badina,Enikö Kövari,Caterina Bendotti,Eleonora Aronica,Carola I. Radulescu,Jia Hui Wong,Anna M. Barron,Amy M. Smith,Samuel J. Barnes,David W. Hampton,Paul van der Valk,Steven Jacobson,Owain W. Howell,David Baker,Markus Kipp,Hannes Kaddatz,Benjamin B. Tournier,Philippe Millet,Paul M. Matthews,Craig S. Moore,Sandra Amor & David R. Owen
Nature Communications Published:28 August 2023
DOI:https://doi.org/10.1038/s41467-023-40937-z
Abstract
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.
