Sökning: WFRF:(Rahman Mahafuzur) >
Binding of Human Pr...
Binding of Human Proteins to Amyloid-beta Protofibrils
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- Rahman, Mahafuzur (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Kemi och Bioteknologi,The Department of Chemistry and Biotechnology
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- Zetterberg, Henrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Lendel, Christofer (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Kemi och Bioteknologi,The Department of Chemistry and Biotechnology
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- Härd, Torleif, 1959 (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Kemi och Bioteknologi,The Department of Chemistry and Biotechnology
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(creator_code:org_t)
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- 2014-12-12
- 2015
- Engelska.
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 10:3, s. 766-774
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- The progressive neurodegeneration in Alzheimers disease is believed to be linked to the presence of prefibrillar aggregates of the amyloid-beta (A beta) peptide in the brain. The exact role of these aggregates in the disease pathology is, however, still an open question. Any mechanism by which oligomeric A beta may cause damage to neuronal cells must, in one way or another, involve interactions with other molecules. Here, we identify proteins in human serum and cerebrospinal fluid that bind to stable protofibrils formed by an engineered variant of A beta 42 (A beta(42CC)). We find that the protofibrils attract a substantial number of protein binding partners. Many of the 101 identified proteins are involved in lipid transport and metabolism, the complement system, or in hemostasis. Binding of representative proteins from all of these groups with micromolar affinity was confirmed using surface plasmon resonance. In addition, binding of apolipoprotein E to the protofibrils with nanomolar affinity was demonstrated. We also find that aggregation of A beta enhances protein binding, as lower amounts of proteins bind monomeric A beta. Proteins that bind to A beta protofibrils might contribute to biological effects in which these aggregates are involved. Our results therefore suggest that an improved understanding of the mechanisms by which A beta causes cytotoxicity and neurodegeneration might be gained from studies carried out in biologically relevant matrices in which A beta-binding proteins are present.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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