The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers
Open accessAbstract
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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Cites
Protein Misfolding, Functional Amyloid, and Human Disease
Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,423
Self-citationProtein folding and misfolding
Dobson, C. M. (2003) · Nature · doi:10.1038/nature02261 · Cited by 4,791
Self-citationSoluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064
Molecular chaperones in cellular protein folding
Hartl, F. U. (1996) · Nature · doi:10.1038/381571a0 · Cited by 3,568
Molecular chaperones in protein folding and proteostasis
Hartl, F. U., Bracher, A., & Hayer-Hartl, M. (2011) · Nature · doi:10.1038/nature10317 · Cited by 3,381
Cedervall, T., Lynch, I., Lindman, S., Berggård, T., Thulin, E., Nilsson, H., Dawson, K. A., & Linse, S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608582104 · Cited by 3,281
Self-citationAdapting Proteostasis for Disease Intervention
Balch, W. E., Morimoto, R. I., Dillin, A., & Kelly, J. W. (2008) · Science · doi:10.1126/science.1141448 · Cited by 2,495
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
Bucciantini, M., Giannoni, E., Chiti, F., Baroni, F., Formigli, L., Zurdo, J., Taddei, N., Ramponi, G., Dobson, C. M., & Stefani, M. (2002) · Nature · doi:10.1038/416507a · Cited by 2,434
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The proteostasis network and its decline in ageing
Hipp, M. S., Kasturi, P., & Hartl, F. U. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0101-y · Cited by 1,642
In vivo aspects of protein folding and quality control
Balchin, D., Hayer-Hartl, M., & Hartl, F. U. (2016) · Science · doi:10.1126/science.aac4354 · Cited by 1,439
Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology
Wei, G., Su, Z., Reynolds, N. P., Arosio, P., Hamley, I. W., Gazit, E., & Mezzenga, R. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00542j · Cited by 904
Self-citationMolecular mechanisms of protein aggregation from global fitting of kinetic models
Meisl, G., Kirkegaard, J. B., Arosio, P., Michaels, T. C. T., Vendruscolo, M., Dobson, C. M., Linse, S., & Knowles, T. P. J. (2016) · Nature Protocols · doi:10.1038/nprot.2016.010 · Cited by 767
Self-citationLee, S. J. C., Nam, E., Lee, H. J., Savelieff, M. G., & Lim, M. H. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00731g · Cited by 576
Metadata
- Authors
- Cohen, S. I. A., Arosio, P., Presto, J., Kurudenkandy, F. R., Biverstål, H., Dolfe, L., Dunning, C., Yang, X., Frohm, B., Vendruscolo, M., Johansson, J., Dobson, C. M., Fisahn, A., Knowles, T. P. J., & Linse, S.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2015-02-16
- Volume
- 22
- Issue
- 3
- Pages
- 207-213
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2141852179
- Cited by
- 414
- References
- 64
- FWCI
- 30.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Cohen, S. I. A., Arosio, P., Presto, J., Kurudenkandy, F. R., Biverstål, H., Dolfe, L., Dunning, C., Yang, X., Frohm, B., Vendruscolo, M., Johansson, J., Dobson, C. M., Fisahn, A., Knowles, T. P. J., & Linse, S. (2015). A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2971
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