Top-down Proteomics: Technology Advancements and Applications to Heart Diseases

Overview

Journal Expert Rev Proteomics

Publisher Informa Healthcare

Date 2016 Jul 25

PMID 27448560

Citations 60

Authors

Wenxuan Cai

Trisha M Tucholski

Zachery R Gregorich

Ying Ge

Affiliations

Soon will be listed here.

Abstract

Introduction: Heart diseases are a leading cause of morbidity and mortality for both men and women worldwide, and impose significant economic burdens on the healthcare systems. Despite substantial effort over the last several decades, the molecular mechanisms underlying diseases of the heart remain poorly understood.

Areas Covered: Altered protein post-translational modifications (PTMs) and protein isoform switching are increasingly recognized as important disease mechanisms. Top-down high-resolution mass spectrometry (MS)-based proteomics has emerged as the most powerful method for the comprehensive analysis of PTMs and protein isoforms. Here, we will review recent technology developments in the field of top-down proteomics, as well as highlight recent studies utilizing top-down proteomics to decipher the cardiac proteome for the understanding of the molecular mechanisms underlying diseases of the heart. Expert commentary: Top-down proteomics is a premier method for the global and comprehensive study of protein isoforms and their PTMs, enabling the identification of novel protein isoforms and PTMs, characterization of sequence variations, and quantification of disease-associated alterations. Despite significant challenges, continuous development of top-down proteomics technology will greatly aid the dissection of the molecular mechanisms underlying diseases of the hearts for the identification of novel biomarkers and therapeutic targets.

Citing Articles

Characterizing age-related changes in intact mitochondrial proteoforms in murine hearts using quantitative top-down proteomics.

Ramirez-Sagredo A, Sunny A, Cupp-Sutton K, Chowdhury T, Zhao Z, Wu S Clin Proteomics. 2024; 21(1):57.

PMID: 39343872 PMC: 11440756. DOI: 10.1186/s12014-024-09509-1.

Toward the analysis of functional proteoforms using mass spectrometry-based stability proteomics.

Kang J, Seshadri M, Cupp-Sutton K, Wu S Front Anal Sci. 2024; 3.

PMID: 39072225 PMC: 11281393. DOI: 10.3389/frans.2023.1186623.

Top-down proteomics.

Roberts D, Loo J, Tsybin Y, Liu X, Wu S, Chamot-Rooke J Nat Rev Methods Primers. 2024; 4(1).

PMID: 39006170 PMC: 11242913. DOI: 10.1038/s43586-024-00318-2.

Multidimensional Separations in Top-Down Proteomics.

Guo Y, Cupp-Sutton K, Zhao Z, Anjum S, Wu S Anal Sci Adv. 2024; 4(5-6):181-203.

PMID: 38188188 PMC: 10769458. DOI: 10.1002/ansa.202300016.

Bromodomain-containing Protein 4 regulates innate inflammation via modulation of alternative splicing.

Mann M, Fu Y, Gearhart R, Xu X, Roberts D, Li Y Front Immunol. 2023; 14:1212770.

PMID: 37435059 PMC: 10331468. DOI: 10.3389/fimmu.2023.1212770.

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