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A molecular chapero...
A molecular chaperone breaks the catalytic cycle that generates toxic Aβ oligomers.
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Cohen, Samuel I A (author)
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Arosio, Paolo (author)
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- Presto, Jenny (author)
- Karolinska Institutet
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- Kurudenkandy, Firoz Roshan (author)
- Karolinska Institutet
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- Biverstål, Henrik (author)
- Karolinska Institutet
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- Dolfe, Lisa (author)
- Karolinska Institutet
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- Dunning, Christopher (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups
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Yang, Xiaoting (author)
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Frohm, Birgitta (author)
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Vendruscolo, Michele (author)
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- Johansson, Jan (author)
- Karolinska Institutet,Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi,Department of Anatomy, Physiology and Biochemistry (AFB),Tallinn University
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Dobson, Christopher M (author)
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- Fisahn, André (author)
- Karolinska Institutet
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Knowles, Tuomas P J (author)
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Linse, Sara (author)
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(creator_code:org_t)
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- 2015-02-16
- 2015
- English.
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In: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9985 .- 1545-9993. ; 22:3, s. 207-213
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Cohen, Samuel I ...
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Arosio, Paolo
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Presto, Jenny
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Kurudenkandy, Fi ...
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Biverstål, Henri ...
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Dolfe, Lisa
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show more...
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Dunning, Christo ...
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Yang, Xiaoting
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Frohm, Birgitta
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Vendruscolo, Mic ...
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Johansson, Jan
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Dobson, Christop ...
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Fisahn, André
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Knowles, Tuomas ...
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Linse, Sara
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Nature Structura ...
- By the university
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Lund University
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Swedish University of Agricultural Sciences
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Karolinska Institutet