Mechanism And Molecular Chaperones In Parkinson's Disease Lesions Protective Effect Of Epilepsy Gene Function Research

Neurodegenerative diseases belong to the most terrible nervous disorders in the world. Parkinson's disease is one of neurodegenerative diseases which afflicted people's life widely. So far, there is no successful clinical treated case of Parkinson's disease and the need to broaden the options for therapy in Parkinson's disease is urgent. This urgency compels renewed focus on the deeper scientific understanding etiology andpathogenesis of the disease. Recently, some work has been performed in this lab. In our study, we overexpressed the α-synuclein in dopaminergic SK-N-SH cells and ThT staining show that α-synuclein forms intracellular aggregates . After examinating the intracellular redox state, we found that there is elevated oxidative state which is resulted from the increase in cytoplasmic dopamine level in cells with α-synuclein overexpression. Heat shock protein 70 belongs to chaperone molecular families and coexpression of hsp70 with α-synuclein can suppress the increase in dopamine level and oxidative state and prevent the neuron cells from death. Co-Immunoprecipitation experiments show the direct interaction between hsp70 and α-synuclein which indicates that hsp70, act as molecular chaperone, may reduce the intracellular aggregation of α-synuclein.Epilepsy is another nervous disorder, which is characterized by thespontaneous recurrent seizure. The mechanism of epileptic spontaneous recurrent seizure is unknown. A rat Epilepsy Related Gene (ERG1), which is the Rattus homologue of NSF(N-ethylmaleimide-Sensitive Fusion protein) family, has been cloned previously in our lab and in the present study we further identified NSF as Epilepsy related gene. We used antisense phosphorothioate oligodeoxynucleotides(PS-ODNs) to suppress the expression of NSF at the mRNA level in primary Hippocampal neurons and then found the neurite outgrowth phenomena, which is similar to the structure changes after Epilepsy. On the other hand, we also found the downregulation expression of NSF during the differentiation of PC12 induced by NGF and high potassium ion. All these together show us that NSF is negatively related with the neurite outgrowth and NSF is an Epilepsy Related Gene.Interleukin-2(IL-2) is one of the key cytokines in the immune systemwhose major function is to stimulate the proliferation of multiple immunocytes. The rapidly activated transcription factor Stat5 is one of the important effectors in the proliferation signal of IL-2.Signal chaperone Hsp90 plays a critical role in many signal transduction pathways that control the cell proliferation. In this study, our experimental results indicate that Hsp90 inhibits the CTLL-2 proliferation control through weakening the phosphorylation of Stat5 and ineracting directly with Stat5.