Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation
| العنوان: | Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation |
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| المؤلفون: | Jin, Meihua, Shiwaku, Hiroki, Tanaka, Hikari, Obita, Takayuki, Ohuchi, Sakurako, Yoshioka, Yuki, Jin, Xiaocen, Kondo, Kanoh, Fujita, Kyota, Homma, Hidenori, Nakajima, Kazuyuki, Mizuguchi, Mineyuki, Okazawa, Hitoshi |
| المصدر: | Nature Communications, Vol 12, Iss 1, Pp 1-22 (2021) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Science, Neuroimmunology, Tau protein, General Physics and Astronomy, Inflammation, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Mice, Interferon, Intracellular receptor, medicine, Animals, Humans, Neurodegeneration, Innate immunity, Mice, Knockout, Membrane Glycoproteins, Multidisciplinary, Innate immune system, Microglia, Binding protein, NF-kappa B, Brain, HIV, Membrane Proteins, Neurodegenerative Diseases, General Chemistry, Alzheimer's disease, medicine.disease, Nucleotidyltransferases, Immunity, Innate, Cell biology, DNA-Binding Proteins, Mice, Inbred C57BL, Tamoxifen, medicine.anatomical_structure, biology.protein, Encephalitis, Female, medicine.symptom, medicine.drug |
| الوصف: | Brain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins by direct interaction and triggers an innate immune response by activating a cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) pathway. Tamoxifen-inducible and microglia-specific depletion of PQBP1 in primary culture in vitro and mouse brain in vivo shows that PQBP1 is essential for sensing-tau to induce nuclear translocation of nuclear factor κB (NFκB), NFκB-dependent transcription of inflammation genes, brain inflammation in vivo, and eventually mouse cognitive impairment. Collectively, PQBP1 is an intracellular receptor in the cGAS-STING pathway not only for cDNA of human immunodeficiency virus (HIV) but also for the transmissible neurodegenerative disease protein tau. This study characterises a mechanism of brain inflammation that is common to virus infection and neurodegenerative disorders. Brain inflammation generally accelerates neurodegeneration but the mechanisms of this are not fully characterised. Here the authors show that PQBP1 in microglia is important for sensing extrinsic Tau 3 R/4 R proteins and triggers an innate immune response through cGAS and STING resulting in cognitive impairment. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0db171981bd9b5b91536f31416be06c8Test https://doi.org/10.1038/s41467-021-26851-2Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0db171981bd9b5b91536f31416be06c8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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