The technological revolution to measure global gene expression at the single-cell level is currently transforming our knowledge of the brain and neurological diseases, leading from a basic understanding of genetic regulators and risk factors to one of more complex gene interactions and biological pathways. Looking ahead, our next challenge will be the reliable measurement and understanding of proteins. We describe in this review how to apply new, powerful methods of protein labeling, tracking, and detection. Recent developments of these methods now enable researchers to uncover protein mechanisms in vivo that may previously have only been hypothesized. These methods are also useful for discovering new biology because how proteins regulate systemic interactions is not well understood in most cases, such as how they travel through the bloodstream to distal targets or cross the blood–brain barrier. Genetic sequencing of DNA and RNA have enabled many great discoveries in the past 20 years, and now, the protein methods described here are creating a more complete picture of how cells to whole organisms function. It is likely that these developments will generate another transformation in biomedical research and our understanding of the brain and will ultimately allow for patient-specific medicine on a protein level.

中文翻译：

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解开蛋白质动力学以了解大脑——下一个分子前沿

在单细胞水平上测量全球基因表达的技术革命目前正在改变我们对大脑和神经系统疾病的认识，从对遗传调节因子和风险因素的基本了解转变为更复杂的基因相互作用和生物途径之一。展望未来，我们的下一个挑战将是对蛋白质的可靠测量和理解。我们在这篇综述中描述了如何应用新的、强大的蛋白质标记、跟踪和检测方法。这些方法的最新发展现在使研究人员能够发现以前可能只是假设的体内蛋白质机制。这些方法对于发现新生物学也很有用，因为在大多数情况下，蛋白质如何调节系统相互作用尚不清楚，例如它们如何通过血流到达远端目标或穿过血脑屏障。在过去的 20 年中，DNA 和 RNA 的基因测序促成了许多重大发现，而现在，这里描述的蛋白质方法正在为细胞与整个生物体的功能创造更完整的画面。这些发展很可能会在生物医学研究和我们对大脑的理解方面产生另一次转变，最终将允许在蛋白质水平上针对患者进行药物治疗。