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基于质谱分析法寻找进展性疾病生物流体生物标志物:淀粉样肽和抗肌萎缩蛋白

Mass spectrometry-based methods for biofluid biomarkers for progressive diseases: amyloid peptides and dystrophins.

作者信息

Niwa Makoto, Noda Kenta, Kobayashi Yoshiyuki, Kageyama Itsuki, Kodama Kota

机构信息

Medical Data Science Laboratory, Hoshi University, Shinagawa, Tokyo, Japan.

Research Organization of Open Innovation and Collaboration, Ritsumeikan University, Ibaraki, Osaka, Japan.

出版信息

Bioanalysis. 2025 May;17(10):671-680. doi: 10.1080/17576180.2025.2515011. Epub 2025 Jun 4.

Abstract

PURPOSE

Using two diseases, Alzheimer's disease and muscular dystrophy as examples, in which many resources have been invested, trends in bioanalytical techniques for detection of peptide or protein biomarkers using mass spectrometry are reviewed using Web of Science database. Amyloid beta peptides have been used to detect Alzheimer's disease, and peptides obtained by tryptic digestion of dystrophin have been used to detect muscular dystrophy. Based on the recent interest in peripheral blood analysis, literature review was focused on biofluid analysis.

RESULTS

Both electrospray or matrix-assisted laser desorption ionization mass spectrometry were employed for amyloid beta peptides, and high-resolution or ion mobility techniques had been introduced to enhance selectivity. Immunoprecipitation techniques were often used for pretreatment; however, emergence of combined use of different solid-phase extraction mode was observed. Regarding tryptic peptides obtained from dystrophin, there are few reported applications in biofluids, and typically electrospray ionization-selected reaction monitoring with pretreatment using solid-phase extraction were employed.

IMPLICATIONS

Validity of blood biomarkers propelled development of bioanalytical methods by attracting research interest. The analytical methodologies was built on proven methods in the field of peptide analysis, and current interests were in techniques increasing selectivity and sensitivity, such as differential mobility spectrometry or parallel reaction monitoring.

摘要

目的

以阿尔茨海默病和肌肉萎缩症这两种投入了大量资源的疾病为例,利用科学网数据库综述使用质谱检测肽或蛋白质生物标志物的生物分析技术的发展趋势。β-淀粉样肽已被用于检测阿尔茨海默病,而经肌营养不良蛋白胰蛋白酶消化得到的肽已被用于检测肌肉萎缩症。基于近期对外周血分析的关注,文献综述聚焦于生物流体分析。

结果

β-淀粉样肽分析采用了电喷雾或基质辅助激光解吸电离质谱,并且引入了高分辨率或离子淌度技术以提高选择性。免疫沉淀技术常用于预处理;然而,也观察到了不同固相萃取模式联合使用的情况。关于从肌营养不良蛋白获得的胰蛋白酶肽,在生物流体中的应用报道较少,通常采用电喷雾电离-选择反应监测并结合固相萃取进行预处理。

启示

血液生物标志物的有效性通过吸引研究兴趣推动了生物分析方法的发展。分析方法基于肽分析领域已证实的方法构建,当前的研究兴趣在于提高选择性和灵敏度的技术,如差分离子淌度谱或平行反应监测。

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