Fahn Stanley, Sulzer David
Department of Neurology, Columbia University, New York, New York 10032, USA.
NeuroRx. 2004 Jan;1(1):139-54. doi: 10.1602/neurorx.1.1.139.
Many of the motoric features that define Parkinson disease (PD) result primarily from the loss of the neuromelanin (NM)-containing dopamine (DA) neurons of the substantia nigra (SN), and to a lesser extent, other mostly catecholaminergic neurons, and are associated with cytoplasmic "Lewy body" inclusions in some of the surviving neurons. While there are uncommon instances of familial PD, and rare instances of known genetic causes, the etiology of the vast majority of PD cases remains unknown (i.e., idiopathic). Here we outline genetic and environmental findings related to PD epidemiology, suggestions that aberrant protein degradation may play a role in disease pathogenesis, and pathogenetic mechanisms including oxidative stress due to DA oxidation that could underlie the selectivity of neurodegeneration. We then outline potential approaches to neuroprotection for PD that are derived from current notions on disease pathogenesis.
许多界定帕金森病（PD）的运动特征主要源于黑质（SN）中含神经黑色素（NM）的多巴胺（DA）神经元的丧失，在较小程度上还源于其他大多为儿茶酚胺能神经元的丧失，并且与一些存活神经元中的细胞质“路易小体”包涵体有关。虽然存在家族性PD的罕见病例以及已知遗传病因的罕见实例，但绝大多数PD病例的病因仍然未知（即特发性）。在这里，我们概述了与PD流行病学相关的遗传和环境研究结果，异常蛋白质降解可能在疾病发病机制中起作用的相关提示，以及包括DA氧化导致的氧化应激等可能是神经变性选择性基础的发病机制。然后，我们概述了源自当前疾病发病机制观念的PD神经保护潜在方法。
