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在阿尔茨海默病和帕金森病中对人类大脑蛋白质组进行全球定量分析。

Global quantitative analysis of the human brain proteome in Alzheimer's and Parkinson's Disease.

机构信息

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.

Center for Neurodegenerative Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.

出版信息

Sci Data. 2018 Mar 13;5:180036. doi: 10.1038/sdata.2018.36.

DOI:10.1038/sdata.2018.36
PMID:29533394
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5848788/
Abstract

Patients with Alzheimer's disease (AD) and Parkinson's disease (PD) often have overlap in clinical presentation and brain neuropathology suggesting that these two diseases share common underlying mechanisms. Currently, the molecular pathways linking AD and PD are incompletely understood. Utilizing Tandem Mass Tag (TMT) isobaric labeling and synchronous precursor selection-based MS3 (SPS-MS3) mass spectrometry, we performed an unbiased quantitative proteomic analysis of post-mortem human brain tissues (n=80) from four different groups defined as controls, AD, PD, and co-morbid AD/PD cases across two brain regions (frontal cortex and anterior cingulate gyrus). In total, we identified 11 840 protein groups representing 10 230 gene symbols, which map to ~65% of the protein coding genes in brain. The utility of including two reference standards in each TMT 10-plex assay to assess intra- and inter-batch variance is also described. Ultimately, this comprehensive human brain proteomic dataset serves as a valuable resource for various research endeavors including, but not limited to, the identification of disease-specific protein signatures and molecular pathways that are common in AD and PD.

摘要

阿尔茨海默病(AD)和帕金森病(PD)患者的临床表现和脑神经病理学常有重叠,表明这两种疾病具有共同的潜在机制。目前,AD 和 PD 之间的分子途径尚不完全清楚。本研究利用串联质量标签(TMT)等压标记和基于同步前体选择的 MS3(SPS-MS3)质谱,对 4 个不同组别的 80 例死后人脑组织(来自额叶皮层和前扣带回两个脑区)进行了无偏定量蛋白质组学分析,这 4 个组分别为对照组、AD 组、PD 组和共患 AD/PD 组。共鉴定到 11840 个蛋白组,代表 10230 个基因符号,这些蛋白组映射到大脑中约 65%的编码蛋白基因。本文还描述了在每个 TMT 10 plex 实验中包含两个参考标准来评估批内和批间差异的实用性。最终,这个全面的人脑蛋白质组数据集可作为各种研究的有价值的资源,包括但不限于鉴定 AD 和 PD 中常见的疾病特异性蛋白特征和分子途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/323a6071e69c/sdata201836-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/2431250659a5/sdata201836-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/dae5a74946ed/sdata201836-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/143ed0a3a3b8/sdata201836-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/323a6071e69c/sdata201836-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/2431250659a5/sdata201836-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/dae5a74946ed/sdata201836-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/143ed0a3a3b8/sdata201836-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a7d/5848788/323a6071e69c/sdata201836-f4.jpg

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