吉林大学中日联谊医院神经科,天津市第四中心医院神经科(天津医科大学第四中心临床学院神经内科),吉林省养蜂科学研究所蜜蜂遗传育种省重点实验室,吉林大学第一医院神经科蛋白质组学实验室
国家自然科学基金资助项目(31050006)
Jilin University,Department of Neurology, Tianjin Fourth Central Hospital (Fourth Central Clinical College of Tianjin Medical University),Key Laboratory for Honeybee Genetics and Queen Breeding, Jilin Provincial Institute of Apicultural Science,Laboratory for Proteomics, Department of Neurology, the First affiliated Hospital, Jilin University
This work was supported by a grant from The National Natural Science Foundation of China (31050006)
原发性帕金森病(idiopathic Parkinson's disease,PD)的主要病理特征之一是出现于中脑特定脑区黑质致密部(substantia nigra pars compacta,SNpc)多巴胺能神经元的路易(小)体(Lewy bodies,LBs),PD病人LBs和/或路易轴突也出现于脑内其他脑区非多巴胺能神经元,比如蓝斑(locus coeruleus,LC)等脑干个别脑区去甲肾上腺素能神经元、额前叶皮层(prefrontal cortex,PFC)、颞叶皮层(temporal cortex,TC)等大脑多个脑区胆碱能神经元.为了明确LBs的蛋白质构成,本文通过蛋白质生物信息学数据分析,就LBs的蛋白质构成归纳了5个方面的要点:a.LBs的组织结构单元是α-突触核蛋白(α-synuclein,α-SYN)表征的2类纤维状聚集物和6类非纤维状聚集物(通常被称为寡聚物);b.病理性α-SYN在LBs内存在5种化学修饰形式;c.19个α-SYN相关蛋白质分别与α-SYN共定位于LBs;d.117个LBs的已知蛋白质被划分为10组不同蛋白质功能群组;e.LBs的蛋白质组学鉴定数据库包含了分别在LC、SNpc和PFC脑区组织水平鉴定的84、124和120个候选蛋白质,在TC脑区细胞水平鉴定的108个候选蛋白质,以及在TC脑区亚细胞水平鉴定的29个候选蛋白质.上述要点广泛、深入地概括了LBs的蛋白质构成.
Lewy bodies (LBs) in dopaminergic neurons in substantia nigra pars compacta (SNpc) are the cardinal pathological hallmark of Parkinson's disease (PD), while LBs and/ or Lewy neurites are also seen in non-dopaminergic neurons in other brain regions of patients with PD, such as noradrenergic neurons in locus coeruleus (LC), and cholinergic neurons in prefrontal cortex (PFC) and temporal cortex (TC). To explicit protein contents of LBs in PD, here is an article that demonstrates five aspects of protein constitution of LBs by analyzing protein bioinformatics datasets related to LBs in PD: (1) LBs is filled with 2 types of alpha-synuclein (α-SYN) positive fibrilar aggregates and/or 6 types of α-SYN positive non-fibrilar aggregates (described frequently in literature as oligomers); (2) modification forms of pathological α-SYN in LBs are often associated with 5 species of chemical modifiers; (3) 19 α-SYN-associated proteins rich in LBs are respectively colocalized with α-SYN; (4) 117 previously reported proteins in LBs in immunochemistry study are at least classified into 10 different groups of functional proteins with close relationship; (5) proteomics database as protein candidate resource for LBs contains 84, 124 and 120 proteins identified respectively from raw tissue samples of LC, SNpc and PFC regions, and 108 proteins identified from a cellular separation of analyte captured from TC region, and 29 proteins identified from a sub-cellular fraction of analyte isolated from TC region. It is suggested that the aforementioned aspects comprehensively and fundamentally reflect protein composition of LBs in PD.
陈加俊,田明秀,李兴安,胡林森.帕金森病路易(小)体的蛋白质生物信息学数据分析[J].生物化学与生物物理进展,2013,40(11):1100-1106
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