COMPLEX I IN PARKINSONS DISEASE

帕金森病（PD）是一种破坏性的神经退行性疾病， 影响了这个国家大约一百万人 首席 症状包括前进性运动缓慢（运动迟缓），震颤， 僵硬和姿势不平衡 PD涉及到 神经元制造多巴胺，一种正常大脑所必需的化学物质 功能 诊断完全是临床的：没有常规的 可用的实验室检查可以确定诊断， 确定性 PD被认为是一种未知的获得性疾病， 病因学 1989年以前的治疗完全是对症治疗 症状，但不是疾病的根本原因。 最近的研究 已经确定了一种酶缺陷患者的血小板线粒体 帕金森氏症。 复合物I活性缺陷的发现 提出了新的调查和治疗策略，但首先， 重要的是要在更大数量和更广泛的范围内证实这一发现， 患者 本项目拟检测血小板线粒体酶 活动：（1）一个较大的群体的典型帕金森氏症患者 疾病（这种酶检测灵敏吗？）; (2)患者 “帕金森+”疾病，具有类似症状但也有额外症状 中枢神经系统退化的迹象（这种酶测定 具体？），(3)PD患者的一级（血亲）亲属（Does 这种酶缺陷似乎是通过线粒体遗传的（母体） 或者它是常染色体显性的，具有降低的遗传率（该性状可能是 父母都有病，但不是所有的人都有病。和 (4)健康的同龄对照组 另外两种酶活性也将 作为对照进行研究，以评估分离的 血小板线粒体 因为需要大量的血小板 对于这些特殊的酶活性，将通过以下方法获得： 血小板去除术，其中血液从体内取出，血小板 分离出来，剩余的血液返回到 志愿者 虽然血小板还没有被认为具有 PD患者的功能缺陷，本项目将解决这一问题 通过对许多PD患者进行功能检查（例如， 聚集率，对活化剂的反应） 以常规方式获得的外周血。 这项研究应该 确定复合物I在每种疾病中的活性范围， 这一发现的敏感性和特异性。 家庭研究将 确定遗传的发生和模式。 血小板功能 研究将确定这些广泛可用的测试是否可以用于 用于筛查高危人群或诊断有问题的人群。 虽然诊断测试的发展将是一个主要的临床 如果能够取得进展，这项工作更重要的潜在成果将是 为新的治疗策略指明方向。 Experimental Therapeutics 正在其他遗传疾病中取代或刺激缺陷 酶;这种策略也可以用于PD。

Parkinson's disease (PD) is a devastating neurodegenerative disease which affects approximately 1 million people in this country. The chief symptoms include advancing slowness of movement (bradykinesia), tremor, rigidity, and postural imbalance. PD involves degeneration of the neurons that make dopamine, a chemical necessary for normal brain function. The diagnosis is entirely clinical: there are no routine laboratory tests available that can establish the diagnosis with certainty. PD has been considered to be an acquired disorder of unknown etiology. Treatment until 1989 has been entirely symptomatic - treating the symptoms but not the root cause of the disease. Very recent research has identified an enzyme defect in platelet mitochondria of patients with Parkinson's disease. The discovery of this defect in complex I activity suggests new investigative and therapeutic strategies, but first it is important to confirm the finding in a larger number and broader range of patients. This project proposes to examine platelet mitochondrial enzyme activity in: (1) a larger group of patients with typical Parkinson's disease (Is this enzyme assay sensitive?); (2) patients with "parkinson-plus" disorders, who have similar symptoms but also additional signs of central nervous system degeneration (Is this enzyme assay specific?), (3) first degree (blood) relatives of patients with PD (Does the enzyme defect appear to be inherited via the mitochondria (maternal) or is it autosomal dominant with reduced penetrance (the trait may be inherited from either parent, but not all who inherit it get sick?)); and (4) healthy, age-matched controls. Two other enzyme activities will also be studied as a control for assessing the overall quality of the isolated platelet mitochondria. Because a large quantity of platelets is required for these special enzyme activities, these will be obtained by plateletpheresis, in which blood is removed from the body, the platelets are separated out, and the remainder of the blood is returned to the volunteer. Although platelets have not been recognized to have functional defects in patients with PD, this project will address this question by screening many patients with PD with functional tests (e.g., rate of aggregation, response to activators) performed on a small sample of peripheral blood obtained in the routine manner. This research should establish the range of complex I activity in each disorder and the sensitivity and specificity of this finding. Family studies will establish the occurrence and pattern of inheritance. Platelet functions studies will establish whether these widely-available tests could be used for screening persons at-risk or those with a questionable diagnosis. Although development of a diagnostic test would be a major clinical advance, the more important potential result of this work would be to point the way to new therapeutic strategies. Experimental therapeutics are under way in other genetic diseases to replace or stimulate defective enzymes; such a strategy could also be pursued for PD.