{"title":"Recent Advances in Mass Spectrometry-Based Studies of Post-translational Modifications in Alzheimer's Disease.","authors":"Feixuan Wu, Wei Li, Haiyan Lu, Lingjun Li","doi":"10.1016/j.mcpro.2025.101003","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. There are over 10 million new cases of AD each year worldwide, implying one new case every 3.2 seconds. Post-translational modifications (PTMs) such as phosphorylation, glycosylation, and citrullination have emerged as key modulators of protein function in AD, influencing protein aggregation, clearance, and toxicity. Mass spectrometry (MS) has become an indispensable tool for detecting and quantifying these PTMs, offering valuable insights into their role in AD pathogenesis. This review explores recent advancements in MS-based studies of PTMs in AD, with emphasis on MS techniques like data-dependent acquisition (DDA) and data-independent acquisition (DIA), as well as enrichment methods used to characterize PTMs. The applications of these MS-based approaches to the study of various PTMs are highlighted, which have significantly accelerated the biomarker discovery process, providing new avenues for early diagnosis and therapeutic targeting. Advances in biological understanding and analytical techniques, while addressing the challenges and future directions, will be discussed.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101003"},"PeriodicalIF":6.1000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular & Cellular Proteomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.mcpro.2025.101003","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline. There are over 10 million new cases of AD each year worldwide, implying one new case every 3.2 seconds. Post-translational modifications (PTMs) such as phosphorylation, glycosylation, and citrullination have emerged as key modulators of protein function in AD, influencing protein aggregation, clearance, and toxicity. Mass spectrometry (MS) has become an indispensable tool for detecting and quantifying these PTMs, offering valuable insights into their role in AD pathogenesis. This review explores recent advancements in MS-based studies of PTMs in AD, with emphasis on MS techniques like data-dependent acquisition (DDA) and data-independent acquisition (DIA), as well as enrichment methods used to characterize PTMs. The applications of these MS-based approaches to the study of various PTMs are highlighted, which have significantly accelerated the biomarker discovery process, providing new avenues for early diagnosis and therapeutic targeting. Advances in biological understanding and analytical techniques, while addressing the challenges and future directions, will be discussed.
期刊介绍:
The mission of MCP is to foster the development and applications of proteomics in both basic and translational research. MCP will publish manuscripts that report significant new biological or clinical discoveries underpinned by proteomic observations across all kingdoms of life. Manuscripts must define the biological roles played by the proteins investigated or their mechanisms of action.
The journal also emphasizes articles that describe innovative new computational methods and technological advancements that will enable future discoveries. Manuscripts describing such approaches do not have to include a solution to a biological problem, but must demonstrate that the technology works as described, is reproducible and is appropriate to uncover yet unknown protein/proteome function or properties using relevant model systems or publicly available data.
Scope:
-Fundamental studies in biology, including integrative "omics" studies, that provide mechanistic insights
-Novel experimental and computational technologies
-Proteogenomic data integration and analysis that enable greater understanding of physiology and disease processes
-Pathway and network analyses of signaling that focus on the roles of post-translational modifications
-Studies of proteome dynamics and quality controls, and their roles in disease
-Studies of evolutionary processes effecting proteome dynamics, quality and regulation
-Chemical proteomics, including mechanisms of drug action
-Proteomics of the immune system and antigen presentation/recognition
-Microbiome proteomics, host-microbe and host-pathogen interactions, and their roles in health and disease
-Clinical and translational studies of human diseases
-Metabolomics to understand functional connections between genes, proteins and phenotypes