English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Inhibition of tau filament formation by conformational modulation.

Akoury, E., Gajda, M., Pickhardt, M., Biernat, J., Pornsuwan, S., Griesinger, C., et al. (2013). Inhibition of tau filament formation by conformational modulation. Journal of the American Chemical Society, 135(7), 2853-2862. doi:10.1021/ja312471h.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-DFE7-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CF13-F
Genre: Journal Article

Files

show Files
hide Files
:
1694103.pdf (Publisher version), 617KB
Name:
1694103.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1694103_si_001.pdf (Publisher version), 7MB
Name:
1694103_si_001.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Akoury, E.1, Author              
Gajda, M., Author
Pickhardt, M., Author
Biernat, J., Author
Pornsuwan, S.2, Author              
Griesinger, C.3, Author              
Mandelkow, E., Author
Zweckstetter, M.1, Author              
Affiliations:
1Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              
2Research Group of Electron Paramagnetic Resonance, MPI for biophysical chemistry, Max Planck Society, ou_578606              
3Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              

Content

show
hide
Free keywords: -
 Abstract: Antiaggregation drugs play an important role in therapeutic approaches for Alzheimer’s disease. Although a large number of small molecules that inhibit the aggregation of the tau protein have been identified, little is known about their mode of action. Here, we reveal the mechanism and the nature of tau species that are generated by interaction of tau with the organic compound pthalocyanine tetrasulfonate (PcTS). We demonstrate that PcTS interferes with tau filament formation by targeting the protein into soluble oligomers. A combination of NMR spectroscopy, electron paramagnetic resonance, and small-angle X-ray scattering reveals that the soluble tau oligomers contain a dynamic, noncooperatively stabilized core with a diameter of 30–40 nm that is distinct from the core of tau filaments. Our results suggest that specific modulation of the conformation of tau is a viable strategy for reduction of pathogenic tau deposits.

Details

show
hide
Language(s): eng - English
 Dates: 2013-01-292013
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/ja312471h
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of the American Chemical Society
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 135 (7) Sequence Number: - Start / End Page: 2853 - 2862 Identifier: -