Parkinson’s disease (PD) is
the second-most prevalent neurodegenerative
disorder in the U.S. α-Synuclein (α-Syn) preformed fibrils
(PFFs) have been shown to propagate PD pathology in neuronal populations.
However, little work has directly characterized the morphological
changes on membranes associated with α-Syn PFFs at a cellular
level. Scanning ion conductance microscopy (SICM) is a noninvasive in situ cell imaging technique and therefore uniquely advantageous
to investigate PFF-induced membrane changes in neuroblastoma cells.
The present work used SICM to monitor cytoplasmic membrane changes
of SH-SY5Y neuroblastoma cells after incubation with varying concentrations
of α-Syn PFFs. Cell membrane roughness significantly increased
as the concentration of α-Syn PFFs increased. Noticeable protrusions
that assumed a more crystalline appearance at higher α-Syn PFF
concentrations were also observed. Cell viability was only slightly
reduced, though statistically significantly, to about 80% but independent
of the dose. These observations indicate that within the 48 h treatment
period, PFFs continue to accumulate on the cell membranes, leading
to membrane roughness increase without causing prominent cell death.
Since PFFs did not induce major cell death, these data suggest that
early interventions targeting fibrils before further aggregation may
prevent the progression of neuron loss in Parkinson’s disease.
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