CFT-PET脑功能成像标准模板的制作与验证

目的 制作CFT-PET脑功能成像标准模板,以便使用统计参数图(SPM)进行统计分析.方法 对11例晚期帕金森病(PD)患者、10名正常人进行CFT-PET显像.用10名正常人的显像数据制作标准模板,并用PD组的数据验证标准模板的可用性.结果 SPM分析结果显示,相对于正常对照组,PD组纹状体两侧仅出现多巴胺转运蛋白(DAT)降低区域,且PD组纹状体受损重的一侧DAT降低区域大于对侧,分析结果证明了模板的可用性.结论 采用本文方法制作的脑功能成像标准模板能够成功分析CFT-PET的成像数据,SPM为一种准确客观的统计分析方法.     

帕金森病伴发快速眼动期睡眠行为障碍患者的临床特点

目的探讨伴发快速眼动期睡眠行为障碍（RBD）帕金森病患者的不同临床特点。方法对47例伴发RBD的帕金森病患者（RBD组）和47例年龄、性别相匹配不伴发RBD的帕金森病对照者（NRBD组）进行对比研究。对两组爱泼沃斯嗜睡量表（ESS）评分、简易智能量表（MMSE）评分、Hoehn—Yahr分期、帕金森综合评分量表（UPDRS）评分、左旋多巴治疗持续时间与剂量、运动并发症等临床特点进行对比分析。结果两组患者的帕金森病发病病程时长、ESS评分、MMSE评分、Hoehn—Yahr分期、UPDRS评分[Я（精神、行为和情绪）,Ⅱ（t3常生活活动）,Ⅲ（运动检查）]之间比较无统计学差异（P〉0．05）。帕金森病RBD组患者较早使用左旋多巴治疗,左旋多巴治疗持续时间较NRBD组长（t=4．24,P=0．04）,使用左旋多巴治疗剂量大（t=8．07,P=0．01）,治疗的并发症（UPDRS评分Ⅳ）与NRBD组相比较显著增加（t=7．20,P=0．01）。结论伴发RBD的帕金森病患者治疗需较早使用左旋多巴制剂且治疗剂量大,进而引发运动并发症（异动症和症状波动）明显增加。     

Mitochondrial activity in the frontal cortex area 8 and angular gyrus in Parkinson's disease and Parkinson's disease with dementia

Altered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression and clinical symptoms such as the presence or absence of dementia. RT‐qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism‐related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle‐aged individuals (MA), and those with incidental PD (iPD), long‐lasting PD with parkinsonism without dementia (PD) and long‐lasting PD with dementia (PDD). Up‐regulation of several genes was found in frontal cortex area 8 in PD when compared with MA and in the angular gyrus in iPD when compared with MA. Marked down‐regulation of genes encoding mitochondrial subunits and energy metabolism‐related enzymes occurs in frontal cortex but only of genes coding for energy metabolism‐related enzymes in the angular gyrus in PDD. Significant decrease in the protein expression levels of several mitochondrial subunits encoded by these genes occurs in frontal cortex area 8 and angular gyrus in PDD. Moreover, expression of MT‐ND1 which is encoded by mitochondrial DNA is also reduced in PDD. Reduced enzymatic activity of complex III in frontal cortex area 8 and angular gyrus is observed in PD, but dramatic reduction in the activity of complexes I, II, II and IV in both regions characterizes PDD. Dementia in the context of PD is linked to region‐specific deregulation of genomic genes encoding subunits of mitochondrial complexes and to marked reduction in the activity of mitochondrial complexes I, II, III and IV.     

Structural and Functional Impact of Parkinson Disease‐Associated Mutations in the E3 Ubiquitin Ligase Parkin

Mutations in the PARKIN/PARK2 gene that result in loss‐of‐function of the encoded, neuroprotective E3 ubiquitin ligase Parkin cause recessive, familial early‐onset Parkinson disease. As an increasing number of rare Parkin sequence variants with unclear pathogenicity are identified, structure–function analyses will be critical to determine their disease relevance. Depending on the specific amino acids affected, several distinct pathomechanisms can result in loss of Parkin function. These include disruption of overall Parkin folding, decreased solubility, and protein aggregation. However pathogenic effects can also result from misregulation of Parkin autoinhibition and of its enzymatic functions. In addition, interference of binding to coenzymes, substrates, and adaptor proteins can affect its catalytic activity too. Herein, we have performed a comprehensive structural and functional analysis of 21 PARK2 missense mutations distributed across the individual protein domains. Using this combined approach, we were able to pinpoint some of the pathogenic mechanisms of individual sequence variants. Similar analyses will be critical in gaining a complete understanding of the complex regulations and enzymatic functions of Parkin. These studies will not only highlight the important residues, but will also help to develop novel therapeutics aimed at activating and preserving an active, neuroprotective form of Parkin.     

Autophagy,its mechanisms and regulation: Implications in neurodegenerative diseases

Autophagy is a major regulatory cellular mechanism which gives the cell an ability to cope with some of the destructive events that normally occur within a metabolically living cell. This is done by maintaining the cellular homeostasis, clearance of damaged organelles and proteins and recycling necessary molecules like amino acids and fatty acids. There is a wide array of factors that influence autophagy in the state of health and disease. Disruption of these mechanisms may not only give rise to several autophagy-related disease, but also it can occur as the result of intracellular changes induced during disease pathogenesis causing exacerbation of the disease. Our knowledge is increasing regarding the role of autophagy and its mechanisms in the pathogenesis of various neurodegenerative diseases such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and Amyotrophic lateral sclerosis. Indeed, getting to know about the pathways of autophagy and its regulation can provide the basis for designing therapeutic interventions. In the present paper, we review the pathways of autophagy, its regulation and the possible autophagy-targeting interventions for the treatment of neurodegenerative disorders.     

龟羚帕安胶囊治疗帕金森病多中心、随机、双盲、对照临床研究

目的 客观评价中药龟羚帕安胶囊治疗帕金森病的临床疗效。     

天麻钩藤饮联合美多巴治疗帕金森临床疗效观察

目的：观察天麻钩藤饮联合关多巴治疗帕金森的临床效果。方法：选择60例帕金森患者为研究对象,随机分成观察组和对照组两组,对照组患者采用美多巴治疗,观察组患者采用天麻钩藤饮联合美多巴治疗,比较两组的治疗效果。结果：观察组患者接受治疗2个月、4个月后,与治疗前相比,其UP—DRS评分、PDQ-39评分均显著降低（P〈0．05）,且观察组患者UPDRS评分、PDQ-39评分均显著低于对照组（P〈0．05）;两组患者睡眠质量评分无统计学差异（P〉0．05）;观察组临床总有效率为86．7％,对照组总有效率为66．7％,观察组临床效果显著优于对照组（P〈0．05）,差异具有统计学意义。结论：天麻钩藤饮联合美多巴治疗帕金森临床疗效显著,可明显改善患者睡眠质量,值得临床推广应用。     

电针对1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病模型小鼠线粒体功能的影响

目的:观察电针对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠行为学、酪氨酸羟化酶(T H)、线粒体复合物Ⅰ — Ⅳ活性、线粒体膜电位、线粒体超微结构的影响,探讨电针治疗PD的可能靶点及机制.方法:将雄性C57BL/6小鼠随机分为对照组、模型组、美多巴组及电针组,每组11只,采用...     

杨志宏教授治疗帕金森病经验

帕金森病是一种多发于中老年的神节系统变性疾病.杨志宏教授治疗帕金森病独具特色,注重滋补肝肾以固本;在化痰祛瘀的同时,注重益气;倡导清热除湿、解毒排毒以护脑;常用解表除湿的方法治疗汗出,疗效显著.     

中西医结合治疗帕金森病研究进展

帕金森病是一种常见的中老年疾病,严重影响病人的生活质量。通过查阅相关中西医结合治疗帕金森病的相关文献,体现中西医对帕金森病的病因、发病机制的认识,药物及外科手术的治疗等方面已取得一定的成效,展现了中西医结合治疗帕金森病的独特优势,但也存在许多不足之处。