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Dissecting the stru...
Dissecting the structural organization of multiprotein amyloid aggregates using a bottom-up approach
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- Chaudhary, Himanshu (författare)
- Current address: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
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- Meister, Sebastian (författare)
- KTH,Proteinteknologi
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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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- Löfblom, John (författare)
- KTH,Proteinvetenskap
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- Lendel, Christofer (författare)
- KTH,Tillämpad fysikalisk kemi
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Current address: Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden Proteinteknologi (creator_code:org_t)
- 2020-04-22
- 2020
- Engelska.
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 11:10, s. 1447-1457
- Relaterad länk:
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https://doi.org/10.1...
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https://pubs.acs.org...
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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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Abstract
Ämnesord
Stäng
- Deposition of fibrillar amyloid β (Aβ) in senile plaques is a pathological signature of Alzheimer's disease. However, senile plaques also contain many other components, including a range of different proteins. Although the composition of the plaques can be analyzed in post mortem tissue, knowledge of the molecular details of these multiprotein inclusions and their assembly processes is limited, which impedes the progress in deciphering the biochemical mechanisms associated with Aβ pathology. We here describe a bottom-up approach to monitor how proteins from human cerebrospinal fluid associate with Aβ amyloid fibrils to form plaque particles. The method combines flow cytometry and mass spectrometry proteomics and allowed us to identify and quantify 128 components of the captured multiprotein aggregates. The results provide insights in the functional characteristics of the sequestered proteins and reveal distinct interactome responses for the two investigated Aβ variants, Aβ(1-40) and Aβ(1-42). Furthermore, the quantitative data is used to build models of the structural organization of the multiprotein aggregates, which suggests that Aβ is not the primary binding target for all the proteins; secondary interactions account for the majority of the assembled components. The study elucidates how different proteins are recruited into senile plaques and establishes a new model system for exploring the pathological mechanisms of Alzheimer's disease from a molecular perspective.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Läkemedelsbioteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Pharmaceutical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- amyloid
- Alzheimer disease
- amyloid
- protein-protein interaction
- flow cytometry
- Alzheimer's disease
- amyloid
- amyloid β
- flow cytometry
- protein-protein interaction
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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