Columbia University College of Physicians and Surgeons, 710 West 168th Street, New York, NY 10032, USA.
Parkinsonism Relat Disord. 2018 Jan;46 Suppl 1:S1-S5. doi: 10.1016/j.parkreldis.2017.07.020. Epub 2017 Aug 1.
It took almost 100 years before a meaningful advance occurred in any basic science understanding of Parkinson disease (PD) following James Parkinson's description in 1817. The Lewy body was described in 1912, and the substantia nigra was found to be depigmented with neuronal loss and gliosis in 1919. The link between dopamine and PD began in 1957, 140 years after Parkinson's Essay. Arvid Carlsson and Oleh Hornykiewicz were the major pioneers. The revolutionary therapeutic breakthrough was the introduction of high dosage levodopa therapy by George Cotzias in 1967. Following 40 years of the dopa/dopamine era, we have entered the era of alpha-synuclein, the protein present in Lewy bodies. Heiko Braak found that alpha-synuclein accumulates initially in the olfactory system and lower brainstem and then travels in an anatomic pattern to involve other regions of the brain and thereby cause progressive symptoms. Alpha-synuclein was somehow converted to a rogue protein. Where this originates and how it is propagated are under intense investigation. At the same time that the alpha-synuclein era was developing, clinical advances took place by recognizing PD as hosting a wide variety of nonmotor features with eventual cognitive impairment in many. Therapeutics has also evolved. Although the most effective therapy for the motor features remains levodopa, surgical approaches and drugs for nonmotor problems continue to expand our ability to treat people with PD. We can expect therapeutic advances in neuroprotection as the basic science discoveries uncovered in the alpha-synuclein era are translated into effective treatments.
帕金森病（PD）的基础科学理解在詹姆斯·帕金森（James Parkinson）于 1817 年描述之后，几乎过了 100 年才取得有意义的进展。1912 年描述了路易体，1919 年发现黑质脱色素伴有神经元丧失和神经胶质增生。多巴胺与 PD 之间的联系始于帕金森论文发表后的 140 年，即 1957 年。阿维德·卡尔森（Arvid Carlsson）和奥莱·豪尼可维茨（Oleh Hornykiewicz）是主要的先驱。革命性的治疗突破是乔治·科茨亚斯（George Cotzias）于 1967 年引入高剂量左旋多巴疗法。在 dopa/dopamine 时代持续了 40 年后，我们进入了 alpha-synuclein 时代，即存在于路易体中的蛋白质。海科·布拉克（Heiko Braak）发现 alpha-synuclein 最初在嗅觉系统和下脑丘中积累，然后以解剖模式传播到大脑的其他区域，从而导致进行性症状。alpha-synuclein 不知何故变成了一种流氓蛋白。这种蛋白起源于何处以及如何传播，正受到深入研究。在 alpha-synuclein 时代发展的同时，临床也取得了进展，即认识到 PD 存在多种非运动特征，最终许多患者会出现认知障碍。治疗方法也在不断发展。虽然左旋多巴仍是治疗运动特征的最有效方法，但手术方法和非运动问题的药物仍在不断扩展我们治疗 PD 患者的能力。随着 alpha-synuclein 时代的基础科学发现转化为有效的治疗方法，我们可以期待神经保护治疗方面的进展。
