Natividad Luis A, Buczynski Matthew W, McClatchy Daniel B, Yates John R
Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA.
School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
Proteomes. 2018 Dec 9;6(4):50. doi: 10.3390/proteomes6040050.
Drug addiction is a complex disorder driven by dysregulation in molecular signaling across several different brain regions. Limited therapeutic options currently exist for treating drug addiction and related psychiatric disorders in clinical populations, largely due to our incomplete understanding of the molecular pathways that influence addiction pathology. Recent work provides strong evidence that addiction-related behaviors emerge from the convergence of many subtle changes in molecular signaling networks that include neuropeptides (neuropeptidome), protein-protein interactions (interactome) and post-translational modifications such as protein phosphorylation (phosphoproteome). Advancements in mass spectrometry methodology are well positioned to identify these novel molecular underpinnings of addiction and further translate these findings into druggable targets for therapeutic development. In this review, we provide a general perspective of the utility of novel mass spectrometry-based approaches for addressing critical questions in addiction neuroscience, highlighting recent innovative studies that exemplify how functional assessments of the neuroproteome can provide insight into the mechanisms of drug addiction.
药物成瘾是一种复杂的疾病，由多个不同脑区分子信号失调所驱动。目前临床人群中治疗药物成瘾及相关精神疾病的治疗选择有限，这主要是因为我们对影响成瘾病理的分子途径了解不全面。最近的研究提供了强有力的证据，表明成瘾相关行为源于分子信号网络中许多细微变化的汇聚，这些变化包括神经肽（神经肽组）、蛋白质 - 蛋白质相互作用（相互作用组）以及蛋白质磷酸化等翻译后修饰（磷酸蛋白质组）。质谱方法的进步非常适合识别成瘾的这些新的分子基础，并将这些发现进一步转化为可用于治疗开发的药物靶点。在本综述中，我们概述了基于质谱的新方法在解决成瘾神经科学关键问题方面的实用性，重点介绍了最近的创新性研究，这些研究例证了神经蛋白质组的功能评估如何能够深入了解药物成瘾的机制。
