Chemical neurobiology of ventral mesencephalon: mechanisms underlying neuronal death in Parkinsonism.

点击翻译按钮获取中文摘要

Parkinson's disease (PD) is a neurodegenerative disease which has profound effects on the Australian community. It affects about 1% of individuals aged more than 50 years and approximately 50,000 Australians. Brain cells die over many years and eventually the loss is so bad from the parts of the brain that coordinate motor control that uncontrollable motor movements occur. The cause of the condition is unknown and although drugs can control the motor disorders for some 5 years, eventually increasing disability occurs and finally complete dependency. The condition has profound effects on the families of the sufferers and the Australian health care system. Clearly, it is most important to understand how brain cells die in this debilitating neurological condition because once this death mechanism is understood then strategies can be devised to protect at risk brain cells so that new drugs can be developed to prevent the onset and progression of the disease. Since post-mortem studies on human brain suggest that cells in Parkinson's disease die by a process of programmed cell death (i.e. an unknown stimulus gives the cells a message to die by an exact mechanism involving gene activation), we shall examine the involvement of this unique form of brain cell death and attempt to determine what factors initiate the process. By establishing experimental models where rat brain cells are cultured, we plan to test how multiple factors could start the death cascade and how possible treatments may be preventitive. These assessments will be performed by measuring cellular biochemistry and electrical activity. We also hope to examine how at risk brain cells can be rescued and stimulated to grow to re-establish normal brain circuits. Overall, the programme aims to understand the disease process such that new directions for its management will be revealed.