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Trodusquemine enhan...
Trodusquemine enhances Aβ42 aggregation but suppresses its toxicity by displacing oligomers from cell membranes
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- Limbocker, Ryan (author)
- University of Cambridge
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- Chia, Sean (author)
- University of Cambridge
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- Ruggeri, Francesco S. (author)
- University of Cambridge
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- Perni, Michele (author)
- University of Cambridge
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- Cascella, Roberta (author)
- University of Florence
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- Heller, Gabriella T. (author)
- University of Cambridge
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- Meisl, Georg (author)
- University of Cambridge
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- Mannini, Benedetta (author)
- University of Cambridge
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- Habchi, Johnny (author)
- University of Cambridge
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- Michaels, Thomas C.T. (author)
- University of Cambridge,Harvard University
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- Challa, Pavan K. (author)
- University of Cambridge
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- Ahn, Minkoo (author)
- University of Cambridge
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- Casford, Samuel T. (author)
- University of Cambridge
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- Fernando, Nilumi (author)
- University of Cambridge
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- Xu, Catherine K. (author)
- University of Cambridge
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- Kloss, Nina D. (author)
- University of Cambridge
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- Cohen, Samuel I.A. (author)
- University of Cambridge
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- Kumita, Janet R. (author)
- University of Cambridge
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- Cecchi, Cristina (author)
- University of Florence
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- Zasloff, Michael (author)
- Georgetown University
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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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- Knowles, Tuomas P.J. (author)
- University of Cambridge
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- Chiti, Fabrizio (author)
- University of Florence
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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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(creator_code:org_t)
- 2019-01-15
- 2019
- English.
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Abstract
Subject headings
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- Transient oligomeric species formed during the aggregation process of the 42-residue form of the amyloid-β peptide (Aβ42) are key pathogenic agents in Alzheimer’s disease (AD). To investigate the relationship between Aβ42 aggregation and its cytotoxicity and the influence of a potential drug on both phenomena, we have studied the effects of trodusquemine. This aminosterol enhances the rate of aggregation by promoting monomer-dependent secondary nucleation, but significantly reduces the toxicity of the resulting oligomers to neuroblastoma cells by inhibiting their binding to the cellular membranes. When administered to a C. elegans model of AD, we again observe an increase in aggregate formation alongside the suppression of Aβ42-induced toxicity. In addition to oligomer displacement, the reduced toxicity could also point towards an increased rate of conversion of oligomers to less toxic fibrils. The ability of a small molecule to reduce the toxicity of oligomeric species represents a potential therapeutic strategy against AD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (subject category)
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- By the author/editor
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Limbocker, Ryan
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Chia, Sean
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Ruggeri, Frances ...
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Perni, Michele
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Cascella, Robert ...
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Heller, Gabriell ...
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show more...
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Meisl, Georg
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Mannini, Benedet ...
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Habchi, Johnny
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Michaels, Thomas ...
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Challa, Pavan K.
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Ahn, Minkoo
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Casford, Samuel ...
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Fernando, Nilumi
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Xu, Catherine K.
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Kloss, Nina D.
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Cohen, Samuel I. ...
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Kumita, Janet R.
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Cecchi, Cristina
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Zasloff, Michael
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Linse, Sara
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Knowles, Tuomas ...
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Chiti, Fabrizio
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Vendruscolo, Mic ...
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Dobson, Christop ...
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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 Medicinal Chemis ...
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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 Cell and Molecul ...
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Nature Communica ...
- By the university
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Lund University