S100A9 amyloid growth and S100A9 fibril-induced impairment of gamma oscillations in area CA3 of mouse hippocampus ex vivo is prevented by Bri2 BRICHOS

Andrade-Talavera, YunieskyNeuronal Oscillations Laboratory, Center for Alzheimer Research, Departments of NVS and KBH, Karolinska Institutet, Solna, Sweden (författare)

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.

Chen, GefeiKarolinska Institutet (författare)
Pansieri, JonathanUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)jopa0120 (författare)
Arroyo-García, Luis EnriqueNeuronal Oscillations Laboratory, Center for Alzheimer Research, Departments of NVS and KBH, Karolinska Institutet, Solna, Sweden (författare)
Toleikis, ZigmantasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania (författare)
Smirnovas, VytautasInstitute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania (författare)
Johansson, JanKarolinska Institutet (författare)
Morozova-Roche, LudmillaUmeå universitet,Institutionen för medicinsk kemi och biofysik(Swepub:umu)lumo0001 (författare)
Fisahn, AndréKarolinska Institutet (författare)
Karolinska InstitutetNeuronal Oscillations Laboratory, Center for Alzheimer Research, Departments of NVS and KBH, Karolinska Institutet, Solna, Sweden (creator_code:org_t)

Av författaren/redakt...: Andrade-Talavera ...; Chen, Gefei; Pansieri, Jonath ...; Arroyo-García, L ...; Toleikis, Zigman ...; Smirnovas, Vytau ...; visa fler...; Johansson, Jan; Morozova-Roche, ...; Fisahn, André; visa färre...

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