Background: PrPC is a host-encoded prion protein, which gets post translationally modified
into a transmissible, β-sheet rich disease associated protein called PrPSc, responsible for the Prion disease
including mad cow disease in cattle and CJD in humans. The PrP 106-126 region in PrPSc peptide
initiates the conformational change in that protein leading to fibrillation. Any agent that can destabilize
or disintegrate such proteins can be served as a potential drug candidate for Prion diseases.
Methods: In the present study, an enzyme Lumbrokinase (LK) was isolated from earthworm and its
activity was exploited towards PrP 106-126 amyloids in vitro along with another enzyme Serratiopeptidase
(SP) taking Nattokinase (NK) as a standard.
Results: The results showed that PrP 106-126 amyloid formation was inhibited by both LK and SP, as
evidenced from Thioflavin T fluorescence assay. Further, the size of fibrils as estimated by dynamic
light scattering, was also found to be lower at different time intervals after incubation of the prion amyloids
with LK and SP. Additionally, the molecular dynamics simulation revealed the thermodynamically
favorable interaction of PrP 106-126 with LK as well as with SP with high affinity.
Conclusion: Finally, the toxicity of the disintegrated amyloids was assessed using PC12 cell lines
which showed higher cell viability in case of LK and SP treated amyloids compared to only PrP 106-
126 amyloid treatment. Altogether, the study concluded that the serine proteases like LK and SP have
the potential to disintegrate PrP 106-126 amyloids with improved cell viability. The in vivo studies are
needed to be executed in future.