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Multivalency drives interactions of alpha-synuclein fibrils with tau

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  • معلومة اضافية
    • بيانات النشر:
      Public Library of Science (PLoS), 2024.
    • الموضوع:
      2024
    • نبذة مختصرة :
      Age-related neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Historically, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and α-synuclein (αS) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may even promote each other’s aggregation. Both tau and αS are intrinsically disordered proteins (IDPs), lacking stable secondary and tertiary structure under physiological conditions. In this study we used a combination of biochemical and biophysical techniques to interrogate the interaction of tau with both soluble and fibrillar αS. Fluorescence correlation spectroscopy (FCS) was used to assess the interactions of specific domains of fluorescently labeled tau with full length and C-terminally truncated αS in both monomer and fibrillar forms. We found that full-length tau as well as individual tau domains interact with monomer αS weakly, but this interaction is much more pronounced with αS aggregates. αS aggregates also mildly slow the rate of tau aggregation, although not the final degree of aggregation. Our findings suggest that co-occurrence of tau and αS in disease are more likely to occur through monomer-fiber binding interactions, rather than monomer-monomer or co-aggregation.
    • ISSN:
      1932-6203
    • الرقم المعرف:
      10.1371/journal.pone.0309416
    • Rights:
      CC BY
      URL: http://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    • الرقم المعرف:
      edsair.doi.dedup.....c4b1192b939b7523026f3fc6b4a151b1