University of Washington, Seattle, WA, USA.
Expert Rev Neurother. 2010 Jun;10(6):925-42. doi: 10.1586/ern.10.54.
Although great effort has been put forth to uncover the complex molecular mechanisms exploited in the pathogenesis of Parkinson's disease, a satisfactory explanation remains to be discovered. The emergence of several -omics techniques, transcriptomics, proteomics and metabolomics, have been integral in confirming previously identified pathways that are associated with dopaminergic neurodegeneration and subsequently Parkinson's disease, including mitochondrial and proteasomal function and synaptic neurotransmission. Additionally, these unbiased techniques, particularly in the brain regions uniquely associated with the disease, have greatly enhanced our ability to identify novel pathways, such as axon-guidance, that are potentially involved in Parkinson's pathogenesis. A comprehensive appraisal of the results obtained by different -omics has also reconfirmed the increase in oxidative stress as a common pathway likely to be critical in Parkinson's development/progression. It is hoped that further integration of these techniques will yield a more comprehensive understanding of Parkinson's disease etiology and the biological pathways that mediate neurodegeneration.
尽管人们已经付出了巨大的努力来揭示帕金森病发病机制中所涉及的复杂分子机制,但仍有待发现令人满意的解释。几种组学技术的出现,包括转录组学、蛋白质组学和代谢组学,对于证实先前与多巴胺能神经退行性变和随后的帕金森病相关的途径至关重要,这些途径包括线粒体和蛋白酶体功能以及突触神经传递。此外,这些无偏技术,特别是在与疾病相关的独特脑区,极大地增强了我们识别新途径的能力,例如轴突导向,这些途径可能与帕金森病的发病机制有关。对不同组学获得的结果的综合评估也再次证实,氧化应激的增加是一种共同途径,可能对帕金森病的发展/进展至关重要。人们希望进一步整合这些技术将产生对帕金森病病因和介导神经退行性变的生物学途径的更全面的理解。