Study On The Expression Of NGF And Related Kinases Before And After Resveratrol Cleared Prion

Prion disease,also known as Transmissible spongiform encephalopathies(TSE),is a type of degenerative disease that affects the central nervous system of humans and animals.It has a long incubation period and a mortality rate of 100%.Neurogrowth factor(NGF)plays an important role in nerve growth,differentiation,development and neuronal survival.Clinical studies have shown that NGF has a certain therapeutic effect on neurodegenerative diseases such as Alzheimer's disease and Parkinson's syndrome,but little research has been done on prion diseases.Recently,resveratrol shows the ability to eliminate prion replication.To obtain insights into the possible changes of brain neurotrophic factor(NGF)and its upstream regulatory cascade during prion infection and after removal of prion propagation,the levels of NGF and its upstream regulatory factors in various SMB cell lines and in the mice brains inoculated with various SMB cellular lysates were assessed with Western blot and.In vitro and in vivo experiments showed that the expression level of NGF was significantly decreased after prion infection,and the NGF content was restored to a certain extent after resveratrol treatment.Morphological assays revealed that the NGF signals mainly colocalized within neurons,but not in the proliferative astrocytes and microglia.The upstream positive regulatory kinases,such as p-CREB,p-Ca MKIV,Ca MKK2 were also remarkably decreased in the prion infected cells and mice brains,whereas the negative regulatory one,p-Ca MKK2,was increased.The aberrant situations of those kinases in prion infected cell lines or mice brains could be also partially reversed by removal of prion agent.Moreover,we demonstrated that the signals of Ca MKK2 and p-Ca MKK2 were also distributed predominately in neurons in the brain tissues.This study demonstrates that NGF and its upstream regulatory kinase abnormalities are directly related to prion infection.Resveratrol has not only the ability to inhibit prion replication,but also to improve the expression of NGF via Ca MKK2/Ca MKIV cascade,which might benefit the microenvironment in brains and provide new ideas for the treatment of prion diseases.