贵州地区苗族人群家族性帕金森病Parkin、PINK1、DJ-1基因的相关性研究

Parkinson's disease (PD) is common in the elderly hereditary degenerative neurological disease. Studies have shown that the incidence of PD is multifactorial environmental and genetic synergy results, the genetic mechanism is considered to be an important factor in PD pathogenesis. PD may be a synergistic effect of multiple genes, genetic heterogeneity is obvious. Because of cultural and geographical reasons, PD genetic mechanisms Miao study has unique conditions. Previous studies suggest that PD patients less than other ethnic peoples of age, a higher incidence of severe symptoms , non-motor symptoms early and obvious , autosomal recessive trend evident , suggesting that the genetic mechanisms of familial PD Miao possible inconsistent with the other races . By cross-sectional survey of Guizhou Miao Autonomous eight PD patients, hospital clinical observation of patients, follow-up, analysis of familial disease genes, we will find mutations structural prediction, database research, microarray analysis, functional analysis. Based on the results of analysis of disease genes for further study the structure, function, building animal models to explore the genetic mechanisms and epidemiological features of the nation PD and establish a platform for genetic diagnosis, revealing the pathogenesis of PD, providing a better guide prevention and treatment for PD patients.

帕金森病（parkinson’s disease,PD）是中老年人常见的神经遗传退行性疾病。研究表明，PD的发病是环境和遗传等多因素协同作用的结果，遗传机制被认为是PD致病的重要因素。PD可能是多基因的协同作用，遗传异质性非常明显。由于文化和地域的原因，贵州苗族的PD遗传机制研究有得天独厚的条件。前期研究提示，该民族PD患者较其他民族发病年龄较轻、发病率较高、症状较重、非运动症状早而明显、常染色体隐性遗传趋势明显，提示贵州苗族家族性PD的遗传机制可能与其他种族不一致。我们通过贵州八个苗族自治县PD患者的横断面调查、医院就诊患者临床观察、随访、家族性致病基因的分析，对发现突变的基因进行结构预测、数据库研究、微阵列分析、功能分析，根据分析的结果进一步研究致病基因的结构、功能、构建动物模型等，探讨该民族PD的遗传机制和流行病学特点，建立基因诊断的平台，揭示PD的致病机理，更好的指导预防和治疗。

帕金森病（parkinson’s disease,PD）是中老年人常见的神经遗传退行性疾病。研究表明，PD的发病是环境和遗传等多因素协同作用的结果，遗传机制被认为是PD致病的重要因素。我们收集了六个县十二个乡镇四十个村三十万的帕金森病例，进行了横断面调查；发表了6篇SCI论文、3篇中文核心期刊、一个专利、四本专著。我们的研究表明上调 miR-375 能够抑制 SP1 ，通过抑制PI3K / Akt信号下调lncRNA UCA1均可减轻多巴胺能神经元的损伤通路改善多巴胺能神经元的损伤，减轻帕金森病大鼠的氧化应激和炎症反应，可能是帕金森病的治疗干预新的靶标。黄芩苷可以通过抗氧化应激，抑制黑质区中多巴胺能神经元的凋亡以及调节单胺神经递质的释放来预防 6-OHDA 诱导的 PD 大鼠的神经变性，为后续研究者了解 PD 的发病机理和药物作用机理提供了依据。