Betarbet Ranjita, Sherer Todd B, Di Monte Donato A, Greenamyre J Timothy
Center for Neurodegenerative Disease and Department of Neurology, Emory University, Atlanta, GA 30322, USA.
Brain Pathol. 2002 Oct;12(4):499-510. doi: 10.1111/j.1750-3639.2002.tb00468.x.
Parkinson's disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration and development of cytoplasmic proteinaceous aggregates known as Lewy bodies. Although the pathogenic mechanisms responsible for PD are not completely understood, many clues have come from biochemical, epidemiological, and genetic studies. Mutations in certain genes found in rare, familial cases of PD, such as alpha-synuclein and parkin, suggest a role for the ubiquitin-proteosome system and aberrant protein aggregation. Biochemical analyses have implicated mitochondrial dysfunction in PD. Epidemiological and animal model studies point to a role for environmental toxins, some of which are mitochondrial inhibitors. Mitochondrial dysfunction, resulting from either genetic defects, environmental exposures or an interaction between the two, may cause alpha-synuclein aggregation or neurodegeneration through oxidative stress or excitotoxicity. A better understanding of the mechanisms underlying PD should reveal novel therapeutic targets.
帕金森病（PD）是一种进行性神经疾病，其特征为黑质纹状体多巴胺能神经元变性以及被称为路易小体的细胞质蛋白质聚集体的形成。尽管导致帕金森病的致病机制尚未完全明确，但许多线索来自生物化学、流行病学及遗传学研究。在罕见的家族性帕金森病病例中发现的某些基因突变，如α-突触核蛋白和帕金蛋白的突变，提示泛素-蛋白酶体系统及异常蛋白质聚集发挥了作用。生物化学分析表明线粒体功能障碍与帕金森病有关。流行病学及动物模型研究指出环境毒素也起到了一定作用，其中一些是线粒体抑制剂。由基因缺陷、环境暴露或两者相互作用导致的线粒体功能障碍，可能通过氧化应激或兴奋性毒性作用引起α-突触核蛋白聚集或神经退行性变。更好地理解帕金森病的潜在机制应能揭示新的治疗靶点。
