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    Home > Biochemistry News > Biotechnology News > Unexpected protein may be messing with your brain

    Unexpected protein may be messing with your brain

    • Last Update: 2022-05-17
    • Source: Internet
    • Author: User
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    Left: The protein TMEM106B, with golf course-like folds
    .
    Right: TMEM106B protein layer by layer to form amyloid fibrils

    .


    Scientists have known for years that amyloid fibrils -- fibrous rope-like structures formed from tightly linked protein molecules -- are present in the brains of people with Alzheimer's and Parkinson's and may play a role in the development of these diseases
    .

    Now, UCLA biochemists have identified such fibrils in the brains of people with frontotemporal lobe degeneration (FTLD)
    .
    FTLD is the most common neurodegenerative disease after Alzheimer's disease and Parkinson's disease

    .
    But surprisingly, the type of protein they expected to find in these potentially harmful fibrils was not present at all; instead, a lesser-known protein, TMEM106B, was thought to be the culprit

    .

    The findings, published in the journal Nature, may spark new attention to TMEM106B in FTLD and similar brain diseases, the researchers said
    .

    Damage to the frontal and temporal lobes of the brain in FTLD occurs earlier than Alzheimer's and Parkinson's, and affects 80 out of every 100,000 people aged 45 to 64 with dementia
    .
    Symptoms include acute changes in behavior and decline in language skills

    .
    The disease the researchers studied is characterized by dense spherical aggregates in brain cells composed of the protein TDP-43

    .

    The UCLA team speculates that if amyloid fibrils were present in the brains of FTLD patients, those fibrils would consist of TDP-43
    .

    Amyloid fibrils were extracted from frozen brain tissue of four deceased patients diagnosed with FTLD-TDP
    .

    However, using a technique called cryo-electron microscopy, or cryo-electron microscopy, they can image large biomolecules in great detail, and together with UCLA bioinformatics researcher Michael Savaya, they determined that these fibrils Consists only of TMEM106B or transmembrane protein 106B
    .

    Even though genetic scientists discovered a decade ago that mutations in this protein were a risk factor for FTLD, senior author Paul Boyle Professor of Molecular Biology at UCLA and Howard Hughes Medical Institute investigator Eisenberg said evidence, but little is known about TMEM106B
    .

    Like a golf course: the structure of amyloid fibrils in FTLD

    According to Eisenberg, who has studied amyloid fibrils for many years, pathological deposits of amyloid have been linked to more than 50 degenerative and potentially fatal diseases
    .

    In a 2005 paper in the journal Nature, Eisenberg and an international team of chemists and molecular biologists reported that these fibers are made of proteins that act like the teeth of a zipper occlusal - recent research has supported this observation
    .
    TMEM106B can form multiple molecular zippers, he said

    .

    Eisenberg noted that the team's structural analysis of TMEM106B fibrils showed that they share the same characteristics as the causative fibrils of Alzheimer's and Parkinson's disease, but are more complex
    .
    Like other fibers, they are stacked in thousands of layers, each of which is composed of individual protein molecules with straight segments and curved corners, folded into complex shapes

    .

    In TMEM106B, the folded protein chain has 18 straight segments, which the researchers likened to the 18 fairways of a golf course -- just like a golf course, where the first and 18th fairways are close to each other
    .
    "So we say TMEM106B has a golf course-like fold," Eisenberg said

    .

    Whether TMEM106B amyloid fibrils lead to FTLD-TDP remains to be seen
    .
    The normal function of the TDP-43 protein is to guide RNA molecules that carry the protein's DNA blueprint from the nucleus into the cytoplasm, and it is unclear what role the TDP-43 protein might play

    .

    "TMEM106B may be one of the causes of FTLD
    .
    In this case, our knowledge of the structure will help in the design of therapeutics," Eisenberg said

    .
    "Further studies may also identify TMEM106B and TDP- 43 links between behaviors

    .
    It is too early to draw conclusions

    .

    "But at the very least, this paper will remind researchers studying neurodegeneration that a new protein may play a potential role," he said
    .

    Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43

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