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Secondary nucleatio...
Secondary nucleation and elongation occur at different sites on Alzheimer's amyloid-b aggregates
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- Scheidt, Tom (author)
- University of Cambridge
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- Łapińska, Urszula (author)
- University of Cambridge
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- Kumita, Janet R. (author)
- University of Cambridge
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- Whiten, Daniel R. (author)
- University of Cambridge,University of Wollongong
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- Klenerman, David (author)
- University of Cambridge
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- Wilson, Mark R. (author)
- University of Wollongong
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- Cohen, Samuel I.A. (author)
- University of Cambridge
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- Linse, Sara (author)
- Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Biokemi och Strukturbiologi,Centrum för Molekylär Proteinvetenskap,Kemiska institutionen,Institutioner vid LTH,Other operations, LTH,Faculty of Engineering, LTH,Biochemistry and Structural Biology,Center for Molecular Protein Science,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Vendruscolo, Michele (author)
- University of Cambridge
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- Dobson, Christopher M. (author)
- University of Cambridge
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- Knowles, Tuomas P.J. (author)
- University of Cambridge
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- Arosio, Paolo (author)
- University of Cambridge,ETH Zürich
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2019
- 2019
- English.
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:4
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Abstract
Subject headings
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- The aggregates of the Ab peptide associated with Alzheimer's disease are able to both grow in size aswell as generate, through secondary nucleation, new small oligomeric species, that are major cytotoxins associated with neuronal death. Despite the importance of these amyloid fibril-dependent processes, their structural and molecular underpinnings have remained challenging to elucidate. Here, we consider two molecular chaperones: The Brichos domain, which suppresses specifically secondary nucleation processes, and clusterin which our results show is capable of inhibiting, specifically, the elongation of Ab fibrils at remarkably low substoichiometric ratios. Microfluidic diffusional sizing measurements demonstrate that this inhibition originates from interactions of clusterin with fibril ends with high affinity. Kinetic experiments in the presence of both molecular chaperones reveal that their inhibitory effects are additive and noncooperative, thereby indicating that the reactive sites associated with the formation of new aggregates and the growth of existing aggregates are distinct.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Scheidt, Tom
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Łapińska, Urszul ...
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Kumita, Janet R.
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Whiten, Daniel R ...
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Klenerman, David
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Wilson, Mark R.
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show more...
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Cohen, Samuel I. ...
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Linse, Sara
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Vendruscolo, Mic ...
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Dobson, Christop ...
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Knowles, Tuomas ...
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Arosio, Paolo
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Science Advances
- By the university
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Lund University