Eve Topf and US National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Department of Pharmacology, Technion-Rappaport Faculty of Medicine, PO Box 9697, Haifa 31096, Israel.
Drug Discov Today. 2004 Dec 15;9(24 Suppl):S37-44.
The remarkable progress made by molecular biology and molecular genetics during the past decade, and the advent of the novel tools of genomics and proteomics, are expected to reveal differential expression profiles of thousands of genes and proteins involved in the degeneration of dopamine-containing cells in Parkinson's disease and allow more focused treatments according to individual genotypes. Of particular interest is the application of microarrays in drug discovery and design to identify 'fingerprints' as potential candidate targets for drug intervention. The major microarray findings relevant to Parkinson's disease and its neurotoxin-induced animal and cell models will be discussed, with particular reference to the neuroprotective therapeutic potential that could arise from the development of drugs 'a la carte'.
在过去十年中,分子生物学和分子遗传学取得了显著的进展,基因组学和蛋白质组学等新工具的出现,有望揭示帕金森病中涉及多巴胺能细胞退化的数千个基因和蛋白质的差异表达谱,并根据个体基因型进行更有针对性的治疗。特别有趣的是将微阵列应用于药物发现和设计中,以识别“指纹”作为药物干预的潜在候选靶点。本文将讨论与帕金森病及其神经毒素诱导的动物和细胞模型相关的主要微阵列发现,并特别参考从“点菜式”药物开发中可能产生的神经保护治疗潜力。