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S100A9 amyloid grow...
S100A9 amyloid growth and S100A9 fibril-induced impairment of gamma oscillations in area CA3 of mouse hippocampus ex vivo is prevented by Bri2 BRICHOS
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- Andrade-Talavera, Yuniesky (author)
- Neuronal Oscillations Laboratory, Center for Alzheimer Research, Departments of NVS and KBH, Karolinska Institutet, Solna, Sweden
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- Chen, Gefei (author)
- Karolinska Institutet
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- Pansieri, Jonathan (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Arroyo-García, Luis Enrique (author)
- Neuronal Oscillations Laboratory, Center for Alzheimer Research, Departments of NVS and KBH, Karolinska Institutet, Solna, Sweden
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- Toleikis, Zigmantas (author)
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
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- Smirnovas, Vytautas (author)
- Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
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- Johansson, Jan (author)
- Karolinska Institutet
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- Morozova-Roche, Ludmilla (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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- Fisahn, André (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Progress in Neurobiology. - : Elsevier. - 0301-0082 .- 1873-5118. ; 219
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- The pro-inflammatory and highly amyloidogenic protein S100A9 is central to the amyloid-neuroinflammatory cascade in neurodegenerative diseases leading to cognitive impairment. Molecular chaperone activity of Bri2 BRICHOS has been demonstrated against a range of amyloidogenic polypeptides. Using a combination of thioflavin T fluorescence kinetic assay, atomic force microscopy and immuno electron microscopy we show here that recombinant Bri2 BRICHOS effectively inhibits S100A9 amyloid growth by capping amyloid fibrils. Using ex-vivo neuronal network electrophysiology in mouse brain slices we also show that both native S100A9 and amyloids of S100A9 disrupt cognition-relevant gamma oscillation power and rhythmicity in hippocampal area CA3 in a time- and protein conformation-dependent manner. Both effects were associated with Toll-like receptor 4 (TLR4) activation and were not observed upon TLR4 blockade. Importantly, S100A9 that had co-aggregated with Bri2 BRICHOS did not elicit degradation of gamma oscillations. Taken together, this work provides insights on the potential influence of S100A9 on cognitive dysfunction in Alzheimer's disease (AD) via gamma oscillation impairment from experimentally-induced gamma oscillations, and further highlights Bri2 BRICHOS as a chaperone against detrimental effects of amyloid self-assembly.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Amyloid
- Bri2 BRICHOS
- Gamma oscillations
- Neurodegeneration
- S100A9
Publication and Content Type
- ref (subject category)
- art (subject category)
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