Parkinson's disease.
Parkinson's disease.
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DOI：
10.1007/978-94-007-5416-4_16
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发表时间：
2012
影响因子：
--
通讯作者：
Maguire-Zeiss, Kathleen A
中科院分区：
文献类型：
--
作者：
Mhyre, Timothy R;Boyd, James T;Hamill, Robert W;Maguire-Zeiss, Kathleen A
帕金森氏病（PD）是最常见的与年龄相关的运动神经退行性疾病，最初在19世纪由詹姆斯·帕金森描述为“颤抖性麻痹”。神经递质多巴胺的缺失被认为是运动功能障碍的病理生理基础；随后，多巴胺替代疗法的发现为PD患者带来了实质性的症状性益处。然而，这些疗法并不能完全治疗临床综合征，也不能改变这种疾病的自然史，这促使临床医生和研究人员进一步研究这种毁灭性疾病的临床表型、病理生理学/病理生物学和病因学。尽管散发性帕金森病的确切病因仍然是个谜，但对家族性和罕见毒性形式的研究为全基因组探索和环境研究奠定了基础。系统的临床评估、系统的病理研究和详细的遗传分析相结合，揭示了PD是一种多面性疾病，具有广泛的临床症状和病理，包括多巴胺系统以外的区域。PD的一个共同线索是存在含有α-突触核蛋白的胞浆内包涵体。α-突触核蛋白的毒性聚集形式（如淀粉样结构）的存在被认为是后续病理的先兆。事实上，PD既是一种脑淀粉样蛋白疾病，也是最常见的突触核蛋白病，即表现为α-突触核蛋白积聚的疾病。在这里，我们介绍了我们目前对帕金森病的病因、病理、临床症状和治疗方法的理解，重点是α-突触核蛋白错误折叠。
Parkinson’s disease (PD) is the most common age-related motoric neurodegenerative disease initially described in the 1800’s by James Parkinson as the ‘Shaking Palsy’. Loss of the neurotransmitter dopamine was recognized as underlying the pathophysiology of the motor dysfunction; subsequently discovery of dopamine replacement therapies brought substantial symptomatic benefit to PD patients. However, these therapies do not fully treat the clinical syndrome nor do they alter the natural history of this disorder motivating clinicians and researchers to further investigate the clinical phenotype, pathophysiology/pathobiology and etiology of this devastating disease. Although the exact cause of sporadic PD remains enigmatic studies of familial and rare toxicant forms of this disorder have laid the foundation for genome wide explorations and environmental studies. The combination of methodical clinical evaluation, systematic pathological studies and detailed genetic analyses have revealed that PD is a multifaceted disorder with a wide-range of clinical symptoms and pathology that include regions outside the dopamine system. One common thread in PD is the presence of intracytoplasmic inclusions that contain the protein, α-synuclein. The presence of toxic aggregated forms of α-synuclein (e.g., amyloid structures) are purported to be a harbinger of subsequent pathology. In fact, PD is both a cerebral amyloid disease and the most common synucleinopathy, that is, diseases that display accumulations of α-synuclein. Here we present our current understanding of PD etiology, pathology, clinical symptoms and therapeutic approaches with an emphasis on misfolded α-synuclein.