Prion peptide 106-126 degradation potential of Serratiopetidase and Lumbrokinase - an in vitro and in silico perspective.

Prion peptide 106-126 degradation potential of Serratiopetidase and Lumbrokinase - an in vitro and in silico perspective. CNS Neurol Disord Drug Targets. 2019 Oct 21;: Authors: Metkar SK, Ghosh S, Girigoswami A, Girigoswami K Abstract 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 cattles and CJD in humans. The PrP 106-126 region in PrPSc peptide initiates the conformational change in that protein leading fibrillation. Any agent that can destabilize or disintegrate such proteins can be served as a potential drug candidate for Prion diseases. In the present study, an enzyme Lumbrokinase (LK) was isolated from earthworm and its activity was exploited towards PrP 106-126 amyloids in vitro alongwith another enzyme Serratiopeptidase (SP) taking Nattokinase (NK) as a standard. 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 reveals the thermodynamically favorable interaction of PrP 106-126 with LK as well as with SP with high affinity. Finally, the toxicity o...
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research