Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients
Upregulation of ribosome complexes at the blood-brain barrier in Alzheimer's disease patients
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DOI：
10.1177/0271678x221111602
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发表时间：
2022-06
影响因子：
6.3
通讯作者：
Masayoshi Suzuki;Kentaro Tezuka;Takumi Handa;Risa Sato;Hina Takeuchi;Masaki Takao;Mitsutoshi Tano;Yasuo Uchida
中科院分区：
文献类型：
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作者：
Masayoshi Suzuki;Kentaro Tezuka;Takumi Handa;Risa Sato;Hina Takeuchi;Masaki Takao;Mitsutoshi Tano;Yasuo Uchida
本研究采用全面、准确的定量蛋白质组学方法，探讨阿尔茨海默病（AD）血管特异性分子机制。从4名AD患者和3名对照供体的脑灰质和白色物质中分离高度纯化的脑毛细血管，并通过SWATH（所有理论碎片离子谱的连续窗口采集）蛋白质组学进行检查。在29种定量的核糖体蛋白中，（RPLP0、RPL4、RPL6、RPL7A、RPL8、RPL10A、RPL11、RPL12、RPL14、RPL15、RPL18、RPL23、RPL27、RPL27A、RPL31、RPL35A、RPS2、RPS3、RPS3A、RPS4X、RPS7、RPS8、RPS14、RPS16、RPS20、RPS24、RPS25、RPS26、RPS28、RPS29、RPS2和RPSA）在AD患者中显著上调。这种核糖体蛋白表达的上调只发生在脑毛细血管中，而不是在脑实质中。内质网中的蛋白质加工和N-糖基化相关蛋白（DDOST、STT 3A、MOGS、GANAB、RPN 1、RPN 2、SEC 61 B、UGGT 1、LMAN 2和SSR 4）的蛋白质表达在AD脑毛细血管中也上调，并且与核糖体蛋白的表达相关。本文报道的研究结果表明，核糖体复合物，随后的蛋白质加工和N-糖基化相关的过程中显着和特异性上调AD患者的脑毛细血管。
The cerebrovascular-specific molecular mechanism in Alzheimer’s disease (AD) was investigated by employing comprehensive and accurate quantitative proteomics. Highly purified brain capillaries were isolated from cerebral gray and white matter of four AD and three control donors, and examined by SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Of the 29 ribosomal proteins that were quantified, 28 (RPLP0, RPL4, RPL6, RPL7A, RPL8, RPL10A, RPL11, RPL12, RPL14, RPL15, RPL18, RPL23, RPL27, RPL27A, RPL31, RPL35A, RPS2, RPS3, RPS3A, RPS4X, RPS7, RPS8, RPS14, RPS16, RPS20, RPS24, RPS25, and RPSA) were significantly upregulated in AD patients. This upregulation of ribosomal protein expression occurred only in brain capillaries and not in brain parenchyma. The protein expression of protein processing and N-glycosylation-related proteins in the endoplasmic reticulum (DDOST, STT3A, MOGS, GANAB, RPN1, RPN2, SEC61B, UGGT1, LMAN2, and SSR4) were also upregulated in AD brain capillaries and was correlated with the expression of ribosomal proteins. The findings reported herein indicate that the ribosome complex, the subsequent protein processing and N-glycosylation-related processes are significantly and specifically upregulated in the brain capillaries of AD patients.