Multivalency drives interactions of alpha-synuclein fibrils with tau

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 pathol...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2024-09, Vol.19 (9), p.e0309416
Main Authors: Ramirez, Jennifer, Saleh, Ibrahim G, Yanagawa, Evan S. K, Shimogawa, Marie, Brackhahn, Emily, Petersson, E. James, Rhoades, Elizabeth
Format: Article
Language:English
Subjects:
Age
Aggregates
Alzheimer's disease
Amino acids
Analysis
Biology and Life Sciences
DNA sequencing
Engineering and Technology
Ethylenediaminetetraacetic acid
Fibrils
Fluorescence spectroscopy
Health aspects
Labeling
Medicine and Health Sciences
Monomers
Movement disorders
Nervous system diseases
Neurodegenerative diseases
Nucleotide sequencing
Parkinson's disease
Pathology
Phosphorylation
Physical Sciences
Physiological aspects
Plasmids
Protein structure
Proteins
Psychological aspects
Research and Analysis Methods
Spectroscopy
Synuclein
Tau protein
Tau proteins
Tertiary structure
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
1932-6203
DOI:10.1371/journal.pone.0309416