Aug 6, 2014

Dityrosine cross-link trapping of amyloid-β intermediates reveals that self-assembly is required for Aβ-induced cytotoxicity

bioRxiv
Bjarki EldonLouise Serpell

Abstract

Multiple chemical reactions, such as the production of reactive oxygen species (ROS) can lead to dityrosine (DiY) formation via the cross-linking of closely spaced tyrosine residues and this can serve as a marker for aging. Amyloid-β (Aβ) has been found to be DiY cross-linked in the brains of AD patients. In vitro, Aβ forms DiY cross-links via metal-catalysed oxidation (Cu2+ and H202) (MCO) leading to the formation of fibrils that are resistant to formic acid denaturation. However, copper is well known to influence and enhance self-assembly. Here, to investigate the interplay between self-assembly and DiY cross-linking we have utilised a non-assembly competent variant of Aβ (vAβ). MCO and UV oxidation experiments using vAβ and wild-type Aβ, revealed that DiY cross-linking stabilises, but does not induce or promote Aβ assembly. Cu2+ alone, without H202, facilitates the formation and DiY cross-linking of wild-type Aβ into long-lived oligomers. Our work reveals DiY formation halts further Aβ self-assembly. DiY cross-linked Aβ is non-toxic to neuroblastoma cells at all stages of self-assembly in contrast to oligomeric non-cross-linked Aβ. These findings point to a mechanism of toxicity that necessitates continuing self-assembly of ...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Genes
Site
Tail
Population Group
Computed (Procedure)
Geneology
Cell Line, Tumor

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Journal of AHIMA
Mary Butter, Maria Campbell
Scientific American
David Biello
British Dental Journal
S B Misra, K J Toumba
BMJ : British Medical Journal
C C Kibbler, S H Gillespie
© 2020 Meta ULC. All rights reserved