Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The chaperone DNAJB6b halts amyloid formation through association with transient Aβ oligomers

Getachew, Josef LU orcid ; Axell, Emil LU ; Carlsson, Andreas LU ; Thacker, Dev LU ; Olsson, Ulf LU orcid and Linse, Sara LU (2026) In Physical Chemistry Chemical Physics 28(19). p.11897-11907
Abstract

Oligomers are transient toxic species in amyloidoses such as Alzheimer's disease. The binding of oligomers by human chaperone proteins has been inferred from the lack of detectable interactions with monomeric amyloid proteins and delay of fibril formation at sub-stoichiometric chaperone to monomer molar ratios. In this study, we provide direct experimental evidence for the binding of the human chaperone DNAJB6b (JB6) to amyloid peptide oligomers formed during an ongoing fibril formation process leading to the stabilization of these transient species. JB6 is a potent inhibitor of the aggregation of multiple amyloid peptides and here we observe the inhibition of the model amyloid-β (Aβ) 20–34 peptide at an astounding sub-stoichiometric 1... (More)

Oligomers are transient toxic species in amyloidoses such as Alzheimer's disease. The binding of oligomers by human chaperone proteins has been inferred from the lack of detectable interactions with monomeric amyloid proteins and delay of fibril formation at sub-stoichiometric chaperone to monomer molar ratios. In this study, we provide direct experimental evidence for the binding of the human chaperone DNAJB6b (JB6) to amyloid peptide oligomers formed during an ongoing fibril formation process leading to the stabilization of these transient species. JB6 is a potent inhibitor of the aggregation of multiple amyloid peptides and here we observe the inhibition of the model amyloid-β (Aβ) 20–34 peptide at an astounding sub-stoichiometric 1 : 100 000 ratio of chaperone to amyloid peptide. Through microfluidic diffusional sizing, we detect an increase in the average hydrodynamic radius of JB6 when added to the supernatant of samples withdrawn from an ongoing fibril formation process, implying an interaction with transient non-monomeric Aβ20–34 and Aβ42 species, which we interpret as oligomers. Furthermore, the oligomer stability towards dissociation was studied using the same method. The results imply that JB6 stabilizes the oligomers against dissociation.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Physical Chemistry Chemical Physics
volume
28
issue
19
pages
11 pages
publisher
Royal Society of Chemistry
external identifiers
  • pmid:42065441
  • scopus:105037655913
ISSN
1463-9076
DOI
10.1039/d6cp00678g
language
English
LU publication?
yes
id
327fcee1-c66e-45dc-a38d-67d45123ce83
date added to LUP
2026-07-09 15:15:13
date last changed
2026-07-23 17:02:05
@article{327fcee1-c66e-45dc-a38d-67d45123ce83,
  abstract     = {{<p>Oligomers are transient toxic species in amyloidoses such as Alzheimer's disease. The binding of oligomers by human chaperone proteins has been inferred from the lack of detectable interactions with monomeric amyloid proteins and delay of fibril formation at sub-stoichiometric chaperone to monomer molar ratios. In this study, we provide direct experimental evidence for the binding of the human chaperone DNAJB6b (JB6) to amyloid peptide oligomers formed during an ongoing fibril formation process leading to the stabilization of these transient species. JB6 is a potent inhibitor of the aggregation of multiple amyloid peptides and here we observe the inhibition of the model amyloid-β (Aβ) 20–34 peptide at an astounding sub-stoichiometric 1 : 100 000 ratio of chaperone to amyloid peptide. Through microfluidic diffusional sizing, we detect an increase in the average hydrodynamic radius of JB6 when added to the supernatant of samples withdrawn from an ongoing fibril formation process, implying an interaction with transient non-monomeric Aβ20–34 and Aβ42 species, which we interpret as oligomers. Furthermore, the oligomer stability towards dissociation was studied using the same method. The results imply that JB6 stabilizes the oligomers against dissociation.</p>}},
  author       = {{Getachew, Josef and Axell, Emil and Carlsson, Andreas and Thacker, Dev and Olsson, Ulf and Linse, Sara}},
  issn         = {{1463-9076}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{19}},
  pages        = {{11897--11907}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Physical Chemistry Chemical Physics}},
  title        = {{The chaperone DNAJB6b halts amyloid formation through association with transient Aβ oligomers}},
  url          = {{http://dx.doi.org/10.1039/d6cp00678g}},
  doi          = {{10.1039/d6cp00678g}},
  volume       = {{28}},
  year         = {{2026}},
}