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FP7

HSP70-TAU NMR Result In Brief

Project ID: 626526
Funded under: FP7-PEOPLE
Country: Germany

Conformational info on neurotoxic proteins

Alzheimer's and Parkinson's diseases are characterised by neurotoxic protein aggregation. EU-funded researchers focused on elucidating the structural changes that lead to tau protein aggregation, a hallmark of Alzheimer's disease.
Conformational info on neurotoxic proteins
Normally, in a disordered conformation, certain stress factors facilitate the transition of tau proteins to an aggregated state. Among these, the molecular chaperones of the heat-shock protein (Hsp) family are believed to play a crucial role. The HSP70-TAU NMR (Structural analysis of the conformational transitions of the K18 fragment of human tau driven by Hsp70 action) initiative employed nuclear magnetic resonance (NMR) spectroscopy to study the interaction between Hsp and tau to identify factors causing protein aggregation.

Researchers comprehensively characterised the binding of the aggregation-prone fragment of tau to two allosteric forms of Hsp70 using NMR experiments along with biophysical and biochemical methods. They successfully determined the tau regions that bind to Hsp70 and Hsp40, and obtained a deeper understanding of the Tau-Hsp40-Hsp70 ternary complex. They found that different Hsp chaperones recognise specific tau regions and this interplay is the key to tau regulation inside a cell.

A first, HSP70-TAU NMR researchers elucidated the binding and activation mechanisms by which Hsp recognises structural changes in misfolded proteins. These findings are invaluable for designing drugs that target tau-binding partners, in other words Hsp, to treat neurodegenerative disorders. Given that over seven million people in the EU suffer from amyloidogenic proteinopathies, discoveries facilitating the development of such potent drugs could significantly reduce the socioeconomic burden of neurodegenerative conditions.

Related information

Keywords

Neurotoxic proteins, Alzheimer's, protein aggregation, tau protein, HSP70-TAU NMR
Record Number: 191050 / Last updated on: 2017-02-09
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