Formation of α-synuclein amyloid fibrils is a pathological hallmark of Parkinson’s disease and a phenomenon that is strongly modulated by environmental factors. Here, we compared effects of different monovalent cations (Li, Na, K) on the formation and properties of α-synuclein amyloid fibrils. Na > Li were found to have concentration-dependent catalytic effects on primary nucleation whereas K ions acted inhibitory. We discuss this discrepancy in terms of a superior affinity of Na and Li to carboxylic protein groups, resulting in reduced Columbic repulsion and by considering K as an ion with poor protein binding and slight chaotropic character, which could promote random coil protein structure. K ions, furthermore, appeared to lower the β-sheet content of the fibrils and increase their persistence lengths, the latter we interpret as a consequence of lesser ion binding and hence higher line charge of the fibrils. The finding that Na and K have opposite effects on α-synuclein aggregation is intriguing in relation to the significant transient gradients of these ions across axonal membranes, but also important for the design and interpretation of biophysical assays where buffers containing these monovalent cations have been intermixedly used.
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