Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain
Proteomic Analysis of Mucopolysaccharidosis IIIB Mouse Brain
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DOI：
10.3390/biom10030355
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发表时间：
2020-03-01
期刊：
影响因子：
5.5
通讯作者：
Caterino, Marianna
中科院分区：
文献类型：
--
作者：
De Pasquale, Valeria;Costanzo, Michele;Caterino, Marianna
粘多糖病IIIB （MPS IIIB）是一种遗传性代谢性疾病，由于α - n -乙酰氨基葡萄糖酶（NAGLU）酶缺乏，随后储存未降解的硫酸肝素（HS）。主要临床表现为重度智力障碍和神经退行性变。采用无标记定量蛋白质组学方法比较MPS IIIB和对照小鼠的脑蛋白质组谱，以确定MPS IIIB改变的神经病理通路。通过自下而上的分析鉴定蛋白质，与野生型（WT）相比，MPS IIIB小鼠大脑中有130个显著代表性不足，74个代表性过高。多种生物信息学分析允许识别三个主要的差异丰富的蛋白质簇：蛋白质参与细胞骨架调节，突触囊泡运输和能量代谢。NAGLU（-/-）小鼠脑的蛋白质组谱可以为进一步研究MPS IIIB的新治疗靶点铺平道路。数据可通过ProteomeXchange获得，标识符为PXD017363。
Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of alpha-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegraded heparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. A label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice to identify altered neuropathological pathways of MPS IIIB. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses allowed to identify three major clusters of the differentially abundant proteins: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The proteome profile of NAGLU(-/-) mouse brain could pave the way for further studies aimed at identifying novel therapeutic targets for the MPS IIIB. Data are available via ProteomeXchange with the identifier PXD017363.