1. Multivalency drives interactions of alpha-synuclein fibrils with tau.
- Author
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Ramirez J, Saleh IG, Yanagawa ESK, Shimogawa M, Brackhahn E, Petersson EJ, and Rhoades E
- Subjects
- Humans, Protein Binding, Protein Aggregates, Amyloid metabolism, Amyloid chemistry, Spectrometry, Fluorescence, Parkinson Disease metabolism, Parkinson Disease pathology, Protein Aggregation, Pathological metabolism, Alzheimer Disease metabolism, Alzheimer Disease pathology, alpha-Synuclein metabolism, alpha-Synuclein chemistry, tau Proteins metabolism, tau Proteins chemistry
- Abstract
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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ramirez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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