The S100A9 protein forms new type of string-like polymeric assemblies
Protein aggregation and activation of inflammatory pathways are common features of age-related neurodegenerative disorders. Conversion of misfolded normally soluble proteins into toxic amyloid aggregates is accompanied by upregulation of pro- inflammatory cytokines such as S100 proteins. S100s are small (10-12kDa) dimeric calcium-binding proteins with a dynamic cellular range of intra and extra cellular concentrations (nM to μM) and oligomeric states (2-8mer and higher) which act via regulatory protein:protein interactions, intracellular Ca2+ sensing and signalling processes in inflammation, proliferation and differentiation, cancer and neurodegeneration.
S100 proteins are consistently deregulated in pathophysiological conditions, including Alzheimer’s Disease (AD). In particular, S100A9 is highly abundant in AD brains1 and has been shown to be a relevant AD biomarker2, being upregulated in Tg2576 AD in connection with memory impairment3. S100A9 interacts with amyloid-beta playing role in its aggregation process4.
We gathered evidence that S100A9 forms stable string-like polymeric structures in vitro under physiological conditions. We hypothesize that these polymers, composed by assembly units which can reversibly dissociate, may be a form of protein stabilisation to maximize its extracellular lifetime in the synaptic environment.
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