疾病简史 张从正，元朝， 《儒门事亲》，“手足震掉，不能持物，抖擞之 状如线引傀儡” ·孙一奎，明朝，《赤水玄珠》，“壮年鲜有，中年以后乃有之， 老年尤多”震颤为主疾病 ·Jame Parkinson:1817,“伴随意肌力减弱的不随意性震颤”作为 一种独立的疾病，《震颤麻痹论》 ·Jean Martin Charcot,I872,发现本病并无肌无力，改称帕金森病
• 张从正，元朝，《儒门事亲》， “手足震掉，不能持物，抖擞之 状如线引傀儡” • 孙一奎，明朝，《赤水玄珠》， “壮年鲜有，中年以后乃有之， 老年尤多”震颤为主疾病 • Jame Parkinson：1817， “伴随意肌力减弱的不随意性震颤”作为 一种独立的疾病，《震颤麻痹论》 • Jean Martin Charcot，1872，发现本病并无肌无力，改称帕金森病。 疾 病 简 史
帕金森病的研究历程 Demonstration that pigmented neurons 8 n可 n the sub Demonstration that First suggestion that the substantia intravenous injection of nigra could be the site of L-DOPA has anti-PD effects Report of marked parkinsonism PDpathology improvement with large oral First neurosurgical intervention doses of DL-DOPA of the basal ganglia to treat PD An Essay on the Demonstration that Shaking Palsy is Recognition of Demonstration of dopamine low oral doses of First attempt at published by post-encephaliti n the brain by histochemical DOPA in huma ans ames Parkinson parkinsonism methods have anti-PD effects 181718721899 1913 1916 1918 191919401957 1958 19601961 1962 1965 1967 198319851988 The shaking palsy is First description First description of Evidence of the Demonstration that First description renamed PD of Lewy bodies neuropathological striatal dopamine mechanical lesions of the of microgliosis in changes in the deficiency in PD striatum cause a loss of the substantia substantia nigra in PD dopamine in the substantia nigra in PD nigra and vice versa Reserpine is reported to reduce motor activity in animals,which was Report of the ALS-PD-dementia Report of a group of drug users reversed by L-DOPA complex of Guam who developed acute parkinson- ism after MPTP exposure Serge Przedborski,2017
帕金森病的研究历程 Serge Przedborski, 2017
帕金森病的研究历程 Demonstration that the direct and Introduction of the direct and Demonstration of efficient indirect pathways are not indirect pathway model of the engraftment of,and motor deficit alternatively but concomitantly basal ganglia circuitry reversal by,dopaminergic neurons active to modulate motor function First double-blind controlled derived from human embryonic Deep brain trial of a cell-based therapy in PD stem cells in an animal model of PD Report suggests that the stimulation of the cell surface molecule subthalamic Mutations in Parkin-PINK1 First phase l LAG3 is a key factor in nucleus becomes SNCA identified as Multiplication reported to clinical trial for the initiation of effective for the Cu of SNCA found requlate immunotherapy a-synuclein cell-to-cell treatment of PD to cause PD mitophagy in PD transmission 1989199019951996 19971998 20012003200420082010 201120122013201420152016 Reversal of GBA mutation identified Direct gener atior monstration of experin ntal clinical trial of as a risk factor for PD n bthalamic glial cell-der First suggestion of iferential cell-to-cell transmissior nouse and eeding and nucleus actor for the of a-synuclein human fibroblasts pathology-inducing treatment of PD capacities Complex I deficit upport found in living animals for the detected in PD d-Synuclein found to be the alternatively active and thus opposite Potential role suggested brains main component of Lewy bodies actions(go versus no go)of the striatal for the microbiome in PD direct and indirect pathways Demonstration of the usefulness of simple asts.to screen for a sms of neurodegeneration Serge Przedborski,2017
帕金森病的研究历程 Serge Przedborski, 2017
病因及发病机制 年龄老化 环境因素 遗传易感性 炎症免疫紊乱 中脑黑质 DA变性 帕金森病 Environmental Health Perspectives 208,121:1245-1251
Environmental Health Perspectives 20139 ,121:1245-1251. 病因及发病机制
病因及发病机制 >环境： 长期接触杀虫剂除草剂工业化学品与PD发病有关 PD模型：用嗜神经毒1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)可制备猴、小鼠PD模型
病因及发病机制 环境： PD模型: 用嗜神经毒1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)可制备猴、小鼠PD模型 长期接触杀虫剂\除草剂\工业化学品与PD发病有关