Press Release

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

Published: November 15, 2021

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.

Journal Article

JOURNAL Nature Communications

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

DOIhttps://doi.org/10.1038/s41467-021-26851-2

Correspondence to

OKAZAWA Hitoshi, M.D., Ph.D., Professor

Department of Neuropathology,
Medical Research Institute,
Tokyo Medical and Dental University(TMDU)
E-mail:okazawa.npat(at)mri.tmd.ac.jp

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