Tsang Fai, Soong Tuck Wah
Ion Channel & Transporter Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.
IUBMB Life. 2003 Jun;55(6):323-7. doi: 10.1080/1521654031000153058.
Parkinson's disease (PD) is a progressive neurodegenerative disease with no known cure and affects approximately 1% of the elderly population. The major question in PD relates to the selective loss of dopaminergic neurons in patients. The underlying mechanism of genetic dysfunction and environmental toxins in contributing to the pathogenesis of PD may be oxidative stress. The interactions of genetic and environmental factors in PD may provide some answers to the longstanding question. In particular, the possibility that iron may provide selectivity to genetic susceptibility or dopamine reactivity in dopaminergic neuronal death is enhanced by the neuroprotection demonstrated in transgenic mice overexpressing ferritin or the use of iron chelators in MPTP-induced PD mouse. It will be important to dissect and understand the contributions of genes, environment and intrinsic cellular states in the generation and progression of the pathophysiology of PD.
帕金森病(PD)是一种进行性神经退行性疾病,目前尚无已知的治愈方法,约影响1%的老年人口。PD的主要问题与患者中多巴胺能神经元的选择性丧失有关。基因功能障碍和环境毒素在PD发病机制中的潜在机制可能是氧化应激。PD中基因和环境因素的相互作用可能为这个长期存在的问题提供一些答案。特别是,在过表达铁蛋白的转基因小鼠中显示的神经保护作用或在MPTP诱导的PD小鼠中使用铁螯合剂,增强了铁可能对多巴胺能神经元死亡中的遗传易感性或多巴胺反应性提供选择性的可能性。剖析和理解基因、环境和内在细胞状态在PD病理生理学的产生和进展中的作用将非常重要。