SH005 - DNAJB1 delays Aβ42 aggregation independently of Hsp70 system

SH005

DNAJB1 delays Aβ42 aggregation independently of Hsp70 system

K. Matulewska-Sobczuk^1,*, D. Thacker¹, U. Olsson¹, S. Linse¹

¹Department of Chemistry, Lund University, Lund, Sweden

 

Rationale: Alzheimer’s disease, one of the most prevalent neurodegenerative diseases, is linked to an impaired protein quality control system and reduced clearance of amyloid fibrils formed by the Aβ42 peptide. We investigate how the co-chaperone DNAJB1 interacts with Aβ42 and influences its aggregation.

Methods: We monitor Aβ42 aggregation kinetics using the amyloid-sensitive fluorescent probe thioflavin T and surface plasmon resonance technology in the presence of DNAJB1 to assess its binding effects. The resulting complexes are characterised using cryo-electron microscopy, biochemical and biophysical methods. In addition, we investigate how different redox conditions modulate the amyloid-chaperone interaction.

Results: We observe that DNAJB1 delays Aβ42 aggregation significantly and that the inhibition changes the amyloid formation process such that it proceeds in multiple macroscopic steps. Our data allow us to propose a possible microscopic mechanism of the inhibition.

Conclusions: These findings provide evidence that DNAJB1 can retard Aβ42 aggregation independently of the HSP70/NEF complex, highlighting its understudied role in prevention of amyloid formation as well as in the clearance pathway.

Disclosure of Interest: None declared