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Search: WFRF:(Cohen I) > Swedish University of Agricultural Sciences

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  • Cohen, Samuel I A, et al. (author)
  • A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.
  • 2015
  • In: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9985 .- 1545-9993. ; 22:3, s. 207-213
  • Journal article (peer-reviewed)abstract
    • Alzheimer's disease is an increasingly prevalent neurodegenerative disorder whose pathogenesis has been associated with aggregation of the amyloid-β peptide (Aβ42). Recent studies have revealed that once Aβ42 fibrils are generated, their surfaces effectively catalyze the formation of neurotoxic oligomers. Here we show that a molecular chaperone, a human Brichos domain, can specifically inhibit this catalytic cycle and limit human Aβ42 toxicity. We demonstrate in vitro that Brichos achieves this inhibition by binding to the surfaces of fibrils, thereby redirecting the aggregation reaction to a pathway that involves minimal formation of toxic oligomeric intermediates. We verify that this mechanism occurs in living mouse brain tissue by cytotoxicity and electrophysiology experiments. These results reveal that molecular chaperones can help maintain protein homeostasis by selectively suppressing critical microscopic steps within the complex reaction pathways responsible for the toxic effects of protein misfolding and aggregation.
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Type of publication
journal article (3)
Type of content
peer-reviewed (3)
Author/Editor
Zhang, Yan (1)
Liu, X (1)
Chen, L (1)
Alonso, A. (1)
Chen, S. (1)
Chen, X. (1)
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Chen, Y. (1)
Donadelli, M. (1)
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Jiang, Y. (1)
Jin, S. (1)
Kim, H. (1)
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Li, Y. (1)
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Wang, K. (1)
Wu, M. (1)
Xu, L. (1)
Yamamoto, A. (1)
Yan, Z. (1)
Yang, H. (1)
Yang, Y. (1)
Yu, J. (1)
Zhang, H. (1)
Zhang, L. (1)
Zhang, X. (1)
Zhang, Z. (1)
Zhou, B. (1)
Zhu, H. (1)
Liu, J. (1)
Zhao, Y. (1)
Lange, C. (1)
Li, X. (1)
Zhao, L. (1)
Liu, C. (1)
Liu, H. (1)
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University
Lund University  (3)Undo refine
Karolinska Institutet (3)
Swedish University of Agricultural Sciences  (3)Undo refine
Umeå University (2)
Stockholm University (2)
Linköping University (2)
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English (3)
Research subject (UKÄ/SCB)
Natural sciences (3)
Medical and Health Sciences (3)

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