The Influence Of Anti-PD-1 On Prion Disease

Prion diseases,also known as the transmissible spongiform encephalopathies,are a group of fatal neurodegenerative disorders,first recorded in the eighteenth century.The prion hypothesis postulates that the infectious agent in prion diseases is a protein,a misfolded conformer of host encoded normal prion protein(PrP^Sc).During the conformational transition:theα-helix content is decreased and theβ-sheet content is increased,which makes the C-terminal of normal prion protein（PrP^C）into a fibrous structure,resulting in partial protease K resistance.This is also an important biochemical indicator for detecting the presence of PrP^Scc in this experiment.（To avoid confusion,in the following sections of this article,PrP is used to refer to normal prion protein,and Prion represents those with pathogenic ability）PD-1,also known as programmed death protein-1,is an important checkpoint molecule,mainly expressed on the surface of activated cytotoxic T cells,which is the negative adjustment switch to prevent the body’s immune response from damaging to the body itself;under normal circumstances,when immune response plays a role,the PD-1 molecule on the surface of the T cell is induced to express and binds the PD-L expressed on the surface of APCs（Antigen presentation cell,APCs）,which down-regulates immune response and acts as a"brake"for the immune response.In this experiment,we use anti-PD-1 to neutralize the PD-1 molecule on the surface of T cells,thereby blocking the PD-1/PD-L signaling pathway to reactivate immune system.In recent years,cancer treatment has been revolutionized by immunotherapy targeting PD-1 expressed mainly on T cells and in this trial we introduced PD-1immunotherapy into prion diseases,hoping to play a therapeutic role in prion diseases.In this class,we firstly used the recombinant prion protein as a substrate to synthesize prion by PMCA and the prion was detected by protease K.Second,we conducted a preliminary experiment to verify the effect of anti-PD-1.Consequently,anti-PD-1 significantly improved the survival condition of melanoma mice.Third,after we intraperitoneally injected 50μl Prion in mice,45 days later,anti-PD-1/IgG were intraperitoneally injected.The results show that average survival time of the mice in the i.p Prion-anti-PD-1 group and the i.p Prion-IgG group was 218days and 216 days,and there was no significant difference.There was also no significant difference in the spongiform change in the brain tissue presented by HE staining,PK-resistant Prion identified by WB and gliosis detected by immunohistochemistry.In summary,anti-PD-1 does not have a significant impact on the pathogenesis and pathological damage of prion diseases.