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  • Chen, G.Karolinska Institutet (author)

Augmentation of Bri2 molecular chaperone activity against amyloid-β reduces neurotoxicity in mouse hippocampus in vitro

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • 2020-01-20
  • Nature Research,2020
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-267767
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-267767URI
  • https://doi.org/10.1038/s42003-020-0757-zDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:142905260URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20200303
  • Molecular chaperones play important roles in preventing protein misfolding and its potentially harmful consequences. Deterioration of molecular chaperone systems upon ageing are thought to underlie age-related neurodegenerative diseases, and augmenting their activities could have therapeutic potential. The dementia relevant domain BRICHOS from the Bri2 protein shows qualitatively different chaperone activities depending on quaternary structure, and assembly of monomers into high-molecular weight oligomers reduces the ability to prevent neurotoxicity induced by the Alzheimer-associated amyloid-β peptide 1-42 (Aβ42). Here we design a Bri2 BRICHOS mutant (R221E) that forms stable monomers and selectively blocks a main source of toxic species during Aβ42 aggregation. Wild type Bri2 BRICHOS oligomers are partly disassembled into monomers in the presence of the R221E mutant, which leads to potentiated ability to prevent Aβ42 toxicity to neuronal network activity. These results suggest that the activity of endogenous molecular chaperones may be modulated to enhance anti-Aβ42 neurotoxic effects.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Andrade-Talavera, Y.Karolinska Institutet (author)
  • Tambaro, S.Karolinska Institutet (author)
  • Leppert, A.Karolinska Institutet (author)
  • Nilsson, Harriet E.KTH,Strukturell bioteknik(Swepub:kth)u1xjilap (author)
  • Zhong, XueyingKTH,Strukturell bioteknik(Swepub:kth)u169038p (author)
  • Landreh, M.Karolinska Institutet (author)
  • Nilsson, P.Karolinska Institutet (author)
  • Hebert, HansKarolinska Institutet,KTH,Strukturell bioteknik(Swepub:kth)u1h8ygcn (author)
  • Biverstål, H. (author)
  • Fisahn, A.Karolinska Institutet (author)
  • Abelein, A.Karolinska Institutet (author)
  • Johansson, J.Karolinska Institutet (author)
  • Karolinska InstitutetStrukturell bioteknik (creator_code:org_t)

Related titles

  • In:Communications Biology: Nature Research3:12399-3642

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