Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation

Meihua Jin, Hiroki Shiwaku, Hikari Tanaka, Takayuki Obita, Sakurako Ohuchi, Yuki Yoshioka, Xiaocen Jin, Kanoh Kondo, Kyota Fujita, Hidenori Homma, Kazuyuki Nakajima, Mineyuki Mizuguchi and Hitoshi Okazawa ()
Additional contact information
Meihua Jin: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Hiroki Shiwaku: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
Hikari Tanaka: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Takayuki Obita: University of Toyama, 2630 Sugitani
Sakurako Ohuchi: University of Toyama, 2630 Sugitani
Yuki Yoshioka: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Xiaocen Jin: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Kanoh Kondo: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Kyota Fujita: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Hidenori Homma: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University
Kazuyuki Nakajima: Institute of Bioinformatics, Soka University
Mineyuki Mizuguchi: University of Toyama, 2630 Sugitani
Hitoshi Okazawa: Medical Research Institute and Center for Brain Integration Research, Tokyo Medical and Dental University

Nature Communications, 2021, vol. 12, issue 1, 1-22

Abstract: Abstract 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26851-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26851-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26851-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().