Xu Long, Sun Haidan, Zhang Yang, Guo Zhengguang, Xiao Xiaoping, Zhou Xin, Hu Kun, Sun Wei, Wang Bo, Liu Weiming
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, South Fourth Ring Road, Beijing, 100070, China.
China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, 100070, China.
Chin Neurosurg J. 2021 May 5;7(1):27. doi: 10.1186/s41016-021-00241-5.
The human brain is the most complex organ in the body, and it is important to have a better understanding of how the protein composition in the brain regions contributes to the pathogenesis of associated neurological disorders.
In this study, a comparative analysis of the frontal and temporal cortex proteomes was conducted by isobaric tags of relative and absolute quantification (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS). Brain protein was taken from relatively normal tissue that could not be avoided of damage during emergent surgery of the TBI (traumatic brain injury) patients admitted in Beijing Tiantan Hospital from 2014 to 2017. Eight cases were included. Four frontal lobes and 4 temporal lobes proteome were analyzed and the proteins were quantitated. Gene Ontology (GO), Ingenuity Pathway Analysis (IPA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the biological function of identified proteins, unchanged proteins, and differentially expressed proteins (DEPs).
A total number of 2127 protein groups were identified in the frontal and temporal lobe proteomes. A total of 1709 proteins could be quantitated in both the frontal and temporal cortex. Among 90 DEPs, 14 proteins were screened highly expressed in the temporal cortex, including MAPT, SNCG, ATP5IF1, GAP43, HSPE1, STMN1, NDUFS6, LDHB, SNCB, NDUFA7, MRPS36, EPDR1, CISD1, and RALA. In addition, compared to proteins expressed in the frontal cortex, 14 proteins including EDC4, NIT2, VWF, ASTN1, TGM2, SSB, CLU, HBA1, STOM, CRP, LRG1, SAA2, S100A4, and VTN were a low expression in the temporal cortex. The biological process enrichment showed that unchanged proteins between the frontal and temporal cortex mainly take part in regulated exocytosis, axon guidance, and vesicle-mediated transport. The KEGG pathway analysis showed that unchanged proteins between the frontal and temporal cortex mainly take part in oxidative phosphorylation, carbon metabolism, Huntington's disease, and Parkinson's disease.
The majority of proteins are unchanged between the frontal and temporal cortex, and unchanged proteins are closely related to its function. Among DEPs, MATP (tau) is upregulated in the temporal cortex, closely related to Alzheimer's disease (AD), and is one of the targets for the treatment of AD. CLU is downregulated in the temporal cortex which functions as an extracellular chaperone that prevents aggregation of non-native proteins. It was suggested that the temporal lobe may not be the "functional dumb area" of the traditional view, but could be involved in important neural metabolic circuits.
人类大脑是人体最复杂的器官，更好地了解脑区中的蛋白质组成如何导致相关神经疾病的发病机制非常重要。
在本研究中，通过相对和绝对定量的等压标签（iTRAQ）标记以及二维液相色谱 - 串联质谱（2D LC-MS/MS）对额叶和颞叶皮质蛋白质组进行了比较分析。脑蛋白取自2014年至2017年在北京天坛医院收治的创伤性脑损伤（TBI）患者急诊手术中不可避免会受到损伤的相对正常的组织。纳入8例患者。分析了4个额叶和4个颞叶的蛋白质组并对蛋白质进行定量。使用基因本体论（GO）、 Ingenuity通路分析（IPA）和京都基因与基因组百科全书（KEGG）通路分析来分析鉴定出的蛋白质、未改变的蛋白质和差异表达蛋白质（DEP）的生物学功能。
在额叶和颞叶蛋白质组中总共鉴定出2127个蛋白质组。在额叶和颞叶皮质中总共可以定量1709种蛋白质。在90个DEP中，筛选出14种在颞叶皮质中高表达的蛋白质，包括MAPT、SNCG、ATP5IF1、GAP43、HSPE1、STMN1、NDUFS6、LDHB、SNCB、NDUFA7、MRPS36、EPDR1、CISD1和RALA。此外，与额叶皮质中表达的蛋白质相比，包括EDC4、NIT2、VWF、ASTN1、TGM2、SSB、CLU、HBA1、STOM、CRP、LRG1、SAA2、S100A4和VTN在内的14种蛋白质在颞叶皮质中低表达。生物学过程富集表明，额叶和颞叶皮质之间未改变的蛋白质主要参与调节性胞吐作用、轴突导向和囊泡介导的运输。KEGG通路分析表明，额叶和颞叶皮质之间未改变的蛋白质主要参与氧化磷酸化、碳代谢、亨廷顿舞蹈病和帕金森病。
额叶和颞叶皮质之间的大多数蛋白质没有变化，且未改变的蛋白质与其功能密切相关。在DEP中，MATP（tau）在颞叶皮质中上调，与阿尔茨海默病（AD）密切相关，是AD治疗的靶点之一。CLU在颞叶皮质中下调，其作为细胞外伴侣可防止非天然蛋白质聚集。提示颞叶可能不是传统观点中的“功能哑区”，而是可能参与重要的神经代谢回路。
