Tuesday, September 28, 2021

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    A central target for treating dementia

    Supercomputer-based dynamic molecular network analysis predicted HMGB1-TLR4-induced signals as the most important targets for two major neurodegenerative dementias. Predictions were validated by significant phenotypic and pathological improvements in four mouse models of frontotemporal lobar degeneration treated with anti-HMGB1 antibody.Credit: Faculty of Neuropathology, Tokyo Medical and Dental University

    Dementia has many faces, and it can be very difficult to treat because it can develop in a variety of ways and can affect patients. But now, using big data supercomputer analysis, Japanese researchers predict that a single protein is a key contributor to the damage caused by two very common forms of dementia. I was able to.

    In a study published this month Communication biology, Researchers at Tokyo Medical and Dental University (TMDU) protein HMGB1 is a key player for both frontotemporal dementia Degeneration And Alzheimer’s disease, Two of the most common causes of dementia.

    Frontotemporal lobar degeneration can be caused by mutations in various genes. This means that one treatment may not be appropriate for all patients. However, because there are some similarities between frontotemporal lobar degeneration and Alzheimer’s disease, researchers at Tokyo Medical and Dental University (TMDU) have asked whether these two conditions cause brain damage in the same way. I investigated.

    “The pathology of Alzheimer’s disease and frontotemporal lobar degeneration often coexist in the postmortem brain,” explains Meihua Jin, the lead author of the study. “Because of this duplication, I wanted to investigate whether the molecular mechanisms of the disease were similar.”

    To do this, researchers used an advanced technique called molecular network analysis to express which proteins and how much in mice genetically engineered to mimic Alzheimer’s disease and frontotemporal lobar degeneration. I took a snapshot of what I was doing. Supercomputer analysis of these protein networks was performed in mice of different ages to dynamically understand how they changed over time.

    “The results were surprisingly clear,” says senior author Hitoshi Okazawa. “We found that the core protein-protein interaction networks of Alzheimer’s disease and frontotemporal lobar degeneration are very similar and share almost 50% of the core nodes.”

    Further analysis of these core protein nodes predicted that signal transduction via HMGB1, a key factor in Alzheimer’s disease, also plays an important role in frontotemporal lobar degeneration. Importantly, this result was confirmed by researchers who found that treating mice with frontotemporal lobar degeneration with antibodies against HMGB1 improved long-term memory. Short-term memory, And spatial memory.

    “Our new method has succeeded in predicting and identifying HMGB1 as an important target for treating patients with dementia due to frontotemporal lobar degeneration, regardless of the genetic basis of the disease.” Says Jin.

    Given the fact that mice recovered memory months after treatment with anti-HMGB1 antibody, treatments targeting this protein could actually reverse the patient’s injury. Frontotemporal lobar degeneration..Because similar molecular changes are found in many different types dementia, Treatment based on this antibody may be effective for a wide range of patients.

    Cerebrospinal fluid biomarkers detect neurodegeneration, Alzheimer’s disease in living patients

    For more information:
    Meihua Jin et al, Prediction and validation of common pathological mechanisms of AD-FTLD based on dynamic molecular network analysis, Communication biology (2021). DOI: 10.1038 / s42003-021-02475-6

    Provided by Tokyo Medical and Dental University

    Quote: One protein that governs all of them: The central target for treating dementia (September 14, 2021) is https: //medicalxpress.com/news/2021-09-protein-central-dementia Obtained from .html on September 14, 2021

    This document is subject to copyright. No part may be reproduced without written permission, except for fair transactions for personal investigation or research purposes. The content is provided for informational purposes only.

    A central target for treating dementia Source link A central target for treating dementia

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