神经精神疾病致病因子的分子机转.pptVIP

神經精神疾病致病因子的分子機轉 牛痘病毒（vaccinia virus, VV）是一種痘病毒，整個病毒的生命週期是在宿主細胞的細胞質中完成。DNA 的基因體（genome）約有192Kb，可以表現出263個病毒蛋白。在多數的細胞中，病毒感染細胞之後會產生病毒後代;然而，在少數細胞中，病毒的生命週期被中止在post-entry的階段，顯示在特定的細胞株中，會有宿主限制的現象產生。對於牛痘病毒來說，在此病毒的其中一種會有宿主限制的細胞株CHO中，牛痘病毒要靠一個宿主範圍基因(host range gene) CP77來完成病毒的生命週期。我的論文主要著重於了解CP77在宿主限制的調控中所扮演的角色。我研究主題的第一部份是要探討CP77在結構及功能上的相關性。我們構築了能表現不同CP77截短片段的重組牛痘病毒，並且在HeLa及CHO細胞中監控這些截短蛋白的表現及測量其穩定性。實驗結果顯示，N端及C端具有保護作用，能在病毒感染的細胞中維持CP77蛋白的穩定性。第二部分是在研究CP77的後修飾轉譯作用。我們發現在病毒感染的HeLa及CHO細胞中，CP77都被ubiquitinated。並且CP77在細胞外也被sumoylated。最後，第三部份，根據之前我們實驗室的酵母菌雙雜交篩選實驗分析結果顯示，一個細胞內蛋白cytidine deaminase (CDA)會與CP77交互作用。在我研究報告中指出，CP77 以及CDA的確在GST-pull down實驗中有交互作用，顯示CDA可能參與調控牛痘病毒宿主限制。 Molecular Risk Factors in Neuropsychiatric Disorders My researches are trying to identify the molecular risk factors in various neuropsychological disorders, including schizophrenia, bipolar mania patients, methamphetamine (MAP) addiction patients and Alzheimer’s disease (AD).The first part of my study was to deal the issue of psychosis in schizophrenia patients and MAP abusers. It is well known that dopaminergic pathway is the major neuronal substrate in the pathophysiology of psychosis development and in the rewarding process of addictive behaviors. The majority of released dopamine is reuptaked by the presynaptic dopamine transporter (DAT) to maintain the homeostasis of dopamine system. It is reasonabe to postulate that hyperdopaminergic state in psychosis might be in part due to the DAT dysfunction. Therefore, we first targeted the association of DAT and psychosis in MAP abusers and schizophrenia patients. One of the DAT gene polymorphism is 40-bp VNTR (variable number tandem repeats) which is located at the 3’-untranslated region of the DAT. However, we did not find the association of this DAT VNTR polymorphism with psychosis, neither in MAP psychosis nor schizophrenia patients. Dopaminergic rewarding system is the main pathway to be activated in addiction behavior. It has been also reported that DRD1A-48G pol