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W6 workshop: How to revive the dead brain Proteomics/Metabolomics

机译:W6研讨会:如何恢复死亡脑蛋白质组学/代谢组学

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Proteomics and metabolomics are very useful tools to detect modifications in protein expression, post-translational modifications of proteins, and variations in the expression of metabolites when comparing control with pathological samples or when analyzing samples subjected to particular experimental conditions. Bioinformatic processing of the results may permit the tracking of altered molecular pathways and discovery of abnormal products linked with pathological states. Additionally, human brain is the principal source of information regarding human neurological diseases; animal models and cells may help to increase understanding about certain, and perhaps crucial, aspects of diseases, but they are not exact models of most human neurodegenerative diseases. This is particularly true when considering Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, schizophrenia and autism, among others. Yet human brains for research are largely obtained after death following generous donation. Concomitant metabolic or systemic diseases together with the conditions of the agonal state may affect different molecules including RNA, microRNAs, proteins, and metabolites. Moreover, post-mortem delay impacts on the molecular preservation of the tissue. A profound understanding of changes related with death and post-mortem conditions is mandatory in order to be able to correctly interpret the data obtained when using post-mortem brain tissue. It is important to know that histone tail acet-ylation is transiently increased in post-mortem brain tissue as it occurs in the areas of penumbra following experimental brain and cardiac infarction. Whether these modifications have an effect on protein synthesis is not known. RNA is also altered in post-mortem brain, and changes largely depend on pre-mortem hazards that have as yet unpredictable regional modifications in a given brain. Protein modifications are well recognized in post-mortem brain, with the vulnerability being variable from one protein to another. More surprising is the observation of increased expression of certain proteins with post-mortem delay indicating not only the possibility of truncation, but also the production of new proteins after death.
机译:蛋白质组学和代谢组学是非常有用的工具,用于检测蛋白质表达,蛋白质后改性的修饰,以及在与病理样品的对照进行对照时或在分析特定实验条件的样品时表达代谢物的变化。结果的生物信息处理可以允许跟踪改变的分子途径和与病理状态相关的异常产物的发现。此外,人脑是人类神经疾病的主要信息来源;动物模型和细胞可能有助于提高对某些疾病的关键方面的理解,但它们并不是大多数人类神经变性疾病的确切模型。当考虑阿尔茨海默病,帕金森病,肌萎缩的外侧硬化,精神分裂症和自闭症等时,这尤其如此。然而,在慷慨捐赠后死亡后,研究的人类大脑在很大程度上得到了。伴随的代谢或全身疾病与曲线状态的条件一起可能影响不同的分子,包括RNA,MicroRNA,蛋白质和代谢物。此外,验尸后延迟对组织分子保存的影响。强烈了解与死亡和验尸条件相关的变化是强制性的,以便能够正确地解释使用后验尸脑组织时获得的数据。重要的是要知道,在实验性大脑和心脏梗死后的Penumbra地区发生后,在验尸脑组织中,组蛋白尾射线射流瞬时增加。这些修饰是否对蛋白质合成具有效果是未知的。 RNA也在后验尸大脑中改变,并且在很大程度上取决于验尸预测危害,其在给定的大脑中具有尚未预测的区域修改。验尸大脑中蛋白质修饰很好地识别,脆弱性从一种蛋白质可变到另一个蛋白质。更令人惊讶的是观察验尸后延迟的某些蛋白质的表达增加,表明不仅是截断的可能性,而且在死亡后的新蛋白质的生产。

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