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Dynamics of oligomer populations formed during the aggregation of Alzheimer's A▫$\beta$▫42 peptideMichaels, Thomas C. T. ...Oligomeric species populated during the aggregation of the A[beta]42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that ... control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of A[beta]42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most A[beta]42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.Vir: Nature chemistry. - ISSN 1755-4349 (12, 2020, str. 445-451)Vrsta gradiva - e-članek ; neleposlovje za odrasleLeto - 2020Jezik - angleškiCOBISS.SI-ID - 13174787
Avtor
Michaels, Thomas C. T. |
Šarić, Anđela, 1985- |
Curk, Samo |
Bernfur, Katja |
Arosio, Paolo |
Meisl, Georg |
Dear, Alexander J. |
Cohen, Samuel I. A. |
Dobson, Christopher M. |
Linse, Sara |
Knowles, Tuomas P. J.
Teme
amiloidne bolezni |
Alzheimerjeva bolezen |
kemijska kinetika |
kemijska fizika |
biofizika |
agregacija proteinov |
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Michaels, Thomas C. T. | ![]() |
Šarić, Anđela, 1985- | ![]() |
Curk, Samo | 40633 |
Bernfur, Katja | ![]() |
Arosio, Paolo | ![]() |
Meisl, Georg | ![]() |
Dear, Alexander J. | ![]() |
Cohen, Samuel I. A. | ![]() |
Dobson, Christopher M. | ![]() |
Linse, Sara | ![]() |
Knowles, Tuomas P. J. | ![]() |
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