Clinical Research Center, Utano National Hospital, National Hospital Organization, 8 Ondoyama-cho, Narutaki, Ukyoku, Kyoto 616-8255, Japan.
Diagnostics (Basel). 2013 Mar 25;3(2):210-21. doi: 10.3390/diagnostics3020210.
Parkinson's disease is the second most prevalent disease of the brain. It is characterized by midbrain dopaminergic neuronal degeneration accompanied by Lewy bodies, intra-cytoplasmic neuronal inclusions that consist mainly of alpha-synuclein. The cardinal motor features are muscular rigidity, bradykinesia, and resting tremor and, in advanced cases, postural instability. Symptoms are relieved by dopamine replacement therapy, but progress slowly. Clinical diagnosis is made according to medical history, neurological examinations and the response to anti-Parkinsonian drugs. There are no laboratory tests for diagnosis of the disease; however, for development of disease-modifying treatment, early diagnosis by objective laboratory test is required. Recently, postsynaptic sympathetic norepinephrine nerve terminals were found to be degenerated as well as mesencephalic dopaminergic neurons. Cardiac norepinephrine denervation can be seen by meta-iodine-benzyl guanidine scintigraphy, and may be a reliable diagnostic marker. Degeneration of norepinephrinergic and dopaminergic neurons suggests that catecholamines may play a central role in the neurodegeneration in Parkinson's disease. Recently several studies showed that alpha-synuclein aggregates in cells exposed to dopamine. Here, we review findings relating to an early diagnostic marker for detecting degeneration of the peripheral sympathetic nerves, and propose the hypothesis that catecholamines cause alpha-synuclein to aggregate and play an important role in disease pathogenesis.
帕金森病是大脑中第二常见的疾病。它的特征是中脑多巴胺能神经元退化，伴有路易体，即主要由α-突触核蛋白组成的细胞质内神经元包涵体。主要的运动特征是肌肉僵硬、运动迟缓、静止性震颤，在晚期还会出现姿势不稳。多巴胺替代疗法可以缓解症状，但病情进展缓慢。临床诊断依据为病史、神经系统检查和抗帕金森药物的反应。目前尚无用于诊断该疾病的实验室检测方法；然而，为了开发疾病修饰治疗方法，需要通过客观的实验室检测进行早期诊断。最近发现，突触后交感去甲肾上腺素神经末梢与中脑多巴胺能神经元一样也发生了退化。间碘苄胍闪烁扫描可观察到心脏去甲肾上腺素神经支配的丧失，这可能是一个可靠的诊断标志物。去甲肾上腺素能和多巴胺能神经元的退化表明儿茶酚胺可能在帕金森病的神经退行性变中起核心作用。最近的几项研究表明，暴露于多巴胺的细胞中α-突触核蛋白聚集。在这里，我们综述了与检测外周交感神经退行性变的早期诊断标志物有关的发现，并提出了儿茶酚胺导致α-突触核蛋白聚集并在疾病发病机制中发挥重要作用的假说。
