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神经系统疾病研究中的系统生物学:聚焦阿尔茨海默病

Systems biology in the study of neurological disorders: focus on Alzheimer's disease.

作者信息

Pasinetti Giulio M, Hiller-Sturmhöfel Susanne

机构信息

Center of Excellence for Research in Complementary and Alternative Medicine in Alzheimer's Disease in the Department of Psychiatry at the Mount Sinai School of Medicine in New York, New York.

出版信息

Alcohol Res Health. 2008;31(1):60-5.

Abstract

Systems biology approaches may be useful for studying the mechanisms underlying alcohol's harmful effects on the brain. Such approaches already are used in the study of Alzheimer's disease (AD), a progressive neurodegenerative disorder that, with the overall increase in life expectancy, will affect an increasing proportion of the population and become an increasingly serious public health concern. Systems biology approaches such as complementary DNA (cDNA) microarray analyses have helped identify several genes whose expression is altered in patients exhibiting the earliest stages of AD. Several of these genes are involved in the release of messenger molecules from the ends of nerve cells (i.e., in synaptic vesicle functioning), and their particular role in AD must be investigated further using conventional molecular biological approaches. Similarly, protein array analyses have identified candidate proteins that may play a role in the development of AD. Finally, proteomic approaches, such as certain mass spectrometry techniques, have been used to search for biomarkers of the progression from normal cognitive functioning to mild cognitive impairment and AD, which eventually may allow early and reliable diagnosis of the disease. These approaches already have yielded some candidate molecules whose validity and reliability as biomarkers of AD, however, still need to be confirmed.

摘要

系统生物学方法可能有助于研究酒精对大脑产生有害影响的潜在机制。此类方法已用于阿尔茨海默病(AD)的研究,AD是一种进行性神经退行性疾病,随着预期寿命的总体增加,将影响越来越多的人口,并成为日益严重的公共卫生问题。诸如互补DNA(cDNA)微阵列分析等系统生物学方法已帮助鉴定出几个基因,其在呈现AD最早阶段的患者中表达发生改变。其中一些基因参与神经细胞末端信使分子的释放(即突触小泡功能),其在AD中的特定作用必须使用传统分子生物学方法进一步研究。同样,蛋白质阵列分析已鉴定出可能在AD发展中起作用的候选蛋白质。最后,蛋白质组学方法,如某些质谱技术,已用于寻找从正常认知功能发展到轻度认知障碍和AD过程中的生物标志物,这最终可能实现该疾病的早期可靠诊断。然而,这些方法已经产生了一些候选分子,其作为AD生物标志物的有效性和可靠性仍有待证实。

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