Tau and PQBP1: protein interaction induces inflammation in the brain

Researchers from Tokyo Medical and Dental University clarified the role of the cell receptor PQBP1 in brain inflammation induced by the neurodegenerative disease protein Tau
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Just as a home security system can alert homeowners of an intruder, a protein called polyglutamine-binding protein-1 (PQBP1) found in brain cells can alert the body to "invading" viruses, such as human immunity.
Defective virus (HIV)
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Now, Japanese researchers have a new understanding of the role of PQBP1 in detecting dysfunctional proteins associated with neurodegenerative diseases

In a new study published in Nature Communications , researchers from Tokyo Medical and Dental University (TMDU ) revealed the role of the intracellular receptor PQBP1 in response to Tau Tau is a protein mainly found in neurons and plays a key role in the progression of neurodegenerative diseases such as Alzheimer's disease
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PQBP1 has previously been shown to be able to sense and bind HIV DNA and trigger an immune pathway called the cGAS-STING pathway to initiate an inflammatory response
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Although PQBP1 has also been shown to interact with dysfunctional proteins, such as those associated with the neurodegenerative disease Huntington’s disease, the specific role of PQBP1 in neurodegenerative inflammation is unclear

"By describing the relationship between PQBP1 and Tau, we were able to elucidate the brain inflammation mechanisms that play a role in viral infections and neurodegenerative diseases," said Hitoshi Okazawa, senior author of the study
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The researchers conducted in vitro analysis using microglia (immune cells expressing PQBP1 found in the brain) to prove that Tau interacts with PQBP1, which drives the immune response by activating the cGAS-STING pathway
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Their research showed that the PQBP1-cGAS-STING pathway works in parallel with the TREM2-mediated pathway, and its mutations are known to be related to Alzheimer's disease

They continued to use a mouse model of conditionally inactivated PQBP1 in microglia, showing that the expression of PQBP1 is necessary for the Tau-induced inflammatory response in the body
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Okazawa said: "We are pleased to find that in the mouse model, the inactivation of PQBP1 in microglia can reduce the brain's response to Tau injection, thereby reducing brain inflammation
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The research team further discovered that mutations in the PQBP1 binding region of the Tau protein reduced the inflammatory response in the brain when the Tau protein was injected
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These findings indicate that PQBP1 may be a potential target for the development of therapeutic drugs for Tau-mediated neurodegenerative diseases

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