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Nanoscale Analysis Reveals the Maturation of Neurodegeneration-Associated Protein Aggregates: Grown in mRNA Granules then Released by Stress Granule Proteins

TDP-43 and FUS are two mRNA-binding proteins associated with neurodegenerative diseases that form cytoplasmic inclusions with prion-like properties in affected neurons. Documenting the early stages of the formation of TDP-43 or FUS protein aggregates and the role of mRNA stress granules that are considered as critical intermediates for protein aggregation is therefore of interest to understand disease propagation. Here, we developed a single molecule approach via atomic force microscopy (AFM), which provides structural information out of reach by fluorescence microscopy. In addition, the aggregation process can be probed in the test tube without separating the interacting partners, which would affect the thermodynamic equilibrium. The results demonstrate that isolated mRNA molecules serve as crucibles to promote TDP-43 and FUS multimerization. Their subsequent merging results in the formation of mRNA granules containing TDP-43 and FUS aggregates. Interestingly, TDP-43 or FUS protein aggregates can be rele...

Authors:   Sanae Abrakhi; Dmitry A. Kretov; Bénédicte Desforges; Ioana Dobra; Ahmed Bouhss; David Pastré; Loic Hamon
Journal:   ACS Nano
Year:   2017
DOI:   10.1021/acsnano.7b03071
Publication date:   05-Jul-2017
Facts, background information, dossiers
  • protein aggregates
  • stress granules
  • stress
  • protein aggregation
  • neurons
  • neurodegenerative diseases
More about American Chemical Society Publications
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