Parkin 基因多态性与散发性帕金森病关系的研究

目的探讨Parkin基因S/N 167多态性与散发性帕金森病(PD)的遗传易感性之间的关系.方法以120例散发性PD患者为研究对象,分为早发性PD组和晚发性PD组,120名正常人作为对照.采用聚合酶链式反应(PCR)扩增所需DNA片段,用限制性内切酶酶切技术测定所研究对象的基因型和等位基因.比较各组间基因型及等位基因频率的差异.结果 PD组与对照组S/N 167多态性等位基因频率无显著性差异(P>0.05);早发性PD组S/N 167多态性等位基因频率显著高于对照组和晚发性PD组(均P<0.05).结论Parkin基因S/N 167多态性可能是早发性PD的危险因素,其患PD的危险性较对照组增高1.69倍.     

Resveratrol Protects against Zearalenone-Induced Mitochondrial Defects during Porcine Oocyte Maturation via PINK1/Parkin-Mediated Mitophagy

Mitochondria hold redox homeostasis and energy metabolism as a crucial factor during oocyte maturation, while the exposure of estrogenic mycotoxin zearalenone causes developmental incapacity in porcine oocyte. This study aimed to reveal a potential resistance of phytoalexin resveratrol against zearalenone during porcine oocyte maturation and whether its mechanism was related with PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Porcine oocytes were exposed to 20 μM zearalenone with or without 2 μM resveratrol during in vitro maturation. As for the results, zearalenone impaired ultrastructure of mitochondria, causing mitochondrial depolarization, oxidative stress, apoptosis and embryonic developmental incapacity, in which mitophagy was induced in response to mitochondrial dysfunction. Phytoalexin resveratrol enhanced mitophagy through PINK1/Parkin in zearalenone-exposed oocytes, manifesting as enhanced mitophagy flux, upregulated PINK1, Parkin, microtubule-associated protein light-chain 3 beta-II (LC3B-II) and downregulated substrates mitofusin 2 (MFN2), voltage-dependent anion channels 1 (VDAC1) and p62 expressions. Resveratrol redressed zearalenone-induced mitochondrial depolarization, oxidative stress and apoptosis, and accelerated mitochondrial DNA copy during maturation, which improved embryonic development. This study offered an antitoxin solution during porcine oocyte maturation and revealed the involvement of PINK1/Parkin-mediated mitophagy, in which resveratrol mitigated zearalenone-induced embryonic developmental incapacity.     

常染色体隐性遗传早发性帕金森病1个家系临床特征及parkin基因突变分析

目的探讨1个常染色体隐性遗传早发性帕金森病（autosomal recessive early-onset parkinson-ism，AREP）家系的临床特征及parkin基因突变情况。方法对1个AREP家系2例患者的临床资料进行回顾性分析，同时应用DNA直接测序、限制性内切酶酶切、荧光半定量PCR等技术方法进行parkin基因的突变分析。结果该家系共2例患者，发病年龄轻，分别为22岁和23岁；病情进展相对缓慢，症状有波动，呈晨轻暮重，腱反射活跃；对小剂量多巴制剂反应良好。基因突变发现该家系存在parkin基因的复合杂合突变（第7号外显子杂合的G859T和第4外显子杂合缺失突变），其中G859T为新报道的点突变。结论我国的AREP家系有帕金森病的一般临床表现，又有其独特的临床特征，存在parkin基因的突变。     

帕金森病所致精神障碍36例临床分析

目的探讨帕金森病所致精神障碍的临床特征、诊断及治疗方法。方法回顾分析36例帕金森病所致精神障碍患者的临床资料。结果帕金森病所致精神障碍以抑郁、焦虑、人格障碍为主要表现。药物及心理治疗总有效率为83．33％。结论帕金森病以出现心境障碍为重要特征,部分病例以抑郁症状为首发。早期干预治疗效果满意。     

家族性帕金森病Parkin基因外显子缺失突变

目的: 研究Parkin基因外显子缺失突变与中国家族性帕金森病(PD)发病的关系,探讨Parkin基因缺失突变在家族性PD发病机制中的作用及与临床特点、手术疗效之间的关系.方法: 家族性PD患者36例为研究对象,正常人20例作为对照,提取外周血白细胞基因组DNA,采用聚合酶链式反应(PCR)扩增目的DNA片段,琼脂糖凝胶电泳检测Parkin基因外显子4,6,7,10缺失情况,观察外显子的缺失分布及缺失率,并结合PD患者的手术疗效分析.结果: 家族性PD患者36例有10例外显子缺失突变,其中外显子4缺失8例,6和7缺失各1例,缺失突变率为27.8%,外显子10未发现异常,对照组中无缺失突变;有外显子缺失突变患者的手术疗效较好.结论: Parkin基因外显子4,6,7缺失突变是我国家族性PD的致病原因之一,PD患者的手术效果与Parkin基因外显子缺失突变与否有关.     

Parkin基因甲基化在鼻咽癌发生发展中的作用

目的探讨Parkin基因甲基化在鼻咽癌发生发展中的作用。方法应用甲基化特异性PCR技术对5个鼻咽癌细胞株（CNE1、CNE2、TW03、HONE1、C666）和1个正常鼻咽上皮细胞株（NP69）、54例鼻咽癌组织和16例正常鼻咽上皮组织的Parkin基因启动子区甲基化状态进行检测,并分析鼻咽癌组织中Parkin基因甲基化与临床特征的关系;应用RT-PCR检测加入甲基转移酶抑制剂（5-氮-2-脱氧胞苷）后CNE1、CNE2中Parkin基因转录表达,分析去甲基化对Parkin基因转录表达的影响。结果1个正常鼻咽上皮细胞株和16例正常鼻咽上皮组织中均未检测到Parkin基因甲基化;5个鼻咽癌细胞株和54例鼻咽癌组织中Parkin基因甲基化频率分别为60.00%和62.96%;54例鼻咽癌患者中Parkin基因甲基化状态与临床因素均无关（均P＞0.05）。经过5-氮-2-脱氧胞苷处理后,Parkin基因在CNE1、CNE2中转录表达增加,分别从0提高至3.65和2.15。结论鼻咽癌中Parkin基因甲基化与转录表达密切相关,是基因表达调节的一种重要方式;可能成为鼻咽癌早期分子生物学辅助诊断的标志物和去甲基化基因治疗的靶点。     

小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及对PINK1/Parkin通路的影响

目的 探讨小檗碱对心肌缺血再灌注损伤大鼠线粒体自噬及PTEN诱导激酶1(PTEN induced putative kinase 1,PINK1)/帕金森病蛋白(Parkin)通路的影响.方法 建立心肌缺血再灌注损伤大鼠模型,随机分组为模型组、小檗碱低、高剂量(75、150 mg/kg)组,自噬抑制剂三甲基腺嘌呤(3-...     

新疆维吾尔族帕金森病患者Parkin基因V/L380多态性研究

目的 研究新疆维吾尔族帕金森病(PD)患者Parkin基因V/L380位点的多态性.方法 提取56例维吾尔族原发性PD患者(PD组)和82例维吾尔族健康对照者(正常对照组)的基因组DNA,采用PCR扩增所需Parkin基因第10外显子基因片段,用限制性内切酶酶切技术检测其Parkin基因V/L380位点的基因型和等位基...     

Nonmotor symptoms in Parkin gene‐related parkinsonism

The aim of the study was to explore the prevalence and differences of nonmotor symptoms (NMSs) in patients with young‐onset Parkinson's disease (YOPD) with and without mutations in the Parkin gene and late‐onset Parkinson's disease (LOPD). Twenty‐seven patients with YOPD and 27 with LOPD, as well as 16 patients with homozygous or compound heterozygote Parkin mutations filled in the nonmotor symptoms questionnaire, a 30‐item self‐completed questionnaire that addresses various NMSs. Overall, NMSs were more prevalent in YOPD (12.07 ± 3.9; P = 0.009) and LOPD (13.26 ± 5.8; P = 0.001) compared with Parkin mutation carriers (7.38 ± 4.2). Dribbling of saliva, vivid dreams, loss of smell, and urinary urgency were more prevalent in YOPD compared with Parkin mutation carriers. Only anxiety was more prevalent in the latter. Apart from anxiety, NMSs appear to be less prevalent in Parkin gene‐related parkinsonism. Although these results need further study, the presented data might be helpful in the clinical recognition of specific phenotypes and genotypes in YOPD. The data are in keeping with a different pathological disease process in Parkin gene‐related parkinsonism. © 2010 Movement Disorder Society