Comparative Proteomics for the Evaluation of Protein Expression and Modifications in Neurodegenerative Diseases

Conti, Antonio; Alessio, Massimo

doi:10.1016/bs.irn.2015.05.004

Cited by 4 publications

(3 citation statements)

References 137 publications

(169 reference statements)

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“…Posttranslational side chain attachments contribute to biogenesis, regulation, and/or activity of many integral membrane proteins, and our understanding of these processes in relation to CFTR has advanced rapidly. Specific PTMs have been implicated as contributors to pathogenesis in numerous clinical settings other than CF, including neoplasia (1,98), heart disease (15,123), infection/inflammation (10,76,179), and neurodegenerative conditions (5,41), among others. The present review highlights a crucial role for covalent protein modifications as part of the CF disease mechanism.…”

Section: Discussionmentioning

confidence: 99%

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

McClure

Barnes

Brodsky

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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Posttranslational modifications add diversity to protein function. Throughout its life cycle, the cystic fibrosis transmembrane conductance regulator (CFTR) undergoes numerous covalent posttranslational modifications (PTMs), including glycosylation, ubiquitination, sumoylation, phosphorylation, and palmitoylation. These modifications regulate key steps during protein biogenesis, such as protein folding, trafficking, stability, function, and association with protein partners and therefore may serve as targets for therapeutic manipulation. More generally, an improved understanding of molecular mechanisms that underlie CFTR PTMs may suggest novel treatment strategies for CF and perhaps other protein conformational diseases. This review provides a comprehensive summary of co- and posttranslational CFTR modifications and their significance with regard to protein biogenesis.

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Section: Discussionmentioning

confidence: 99%

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

McClure

Barnes

Brodsky

et al. 2016

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…For biomarker discovery, comparative proteomics using a combination of 2‐dimensional (2D) electrophoresis and MALDI‐TOF MS has been extensively used for discovery of biomarkers over the last 30 years . Brain natriuretic peptide (BNP) and serum amyloid P‐component were discovered for AMI biomarkers using 2D analysis .…”

Section: Introductionmentioning

confidence: 99%

Obscurin and Clusterin Elevation in Serum of Acute Myocardial Infarction Patients

Kang

Seong

Mahmud

et al. 2020

Bulletin Korean Chem Soc

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We discovered new biomarker candidates for acute myocardial infarction (AMI) using micro LC and accurate mass spectrometry. Two serum samples were pooled and used for biomarker screening. UHPLC‐LTQ‐Orbitrap analysis was used with data‐dependent acquisition followed by Sequest search. Six biomarker candidates were selected after fold change analysis of peptides in AMI patient samples compared to healthy controls. Literature search results were reflected. The six biomarker candidates were characterized and quantified using multi reaction monitoring using synthesized peptides or trypsin digested protein standards. Levels of obscurin, alpha‐1‐acid glycoprotein 1, and clusterin were significantly increased (p < 0.001) in AMI patient samples compared to levels in healthy controls, while those of antithrombin III and fibrinogen beta were not. We confirmed the diagnostic performance of obscurin and clusterin as biomarker candidates for AMI using commercial ELISA kits. Receiver operating characteristic results showed that obscurin and clusterin showed highest sensitivity and specificity for AMI diagnosis together with troponins by both of multi‐reaction monitoring analysis and ELISA.

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“…The analysis of PTMs usually combines 2DE protein separation with complementary biochemical assays that exploit specific enzymes or chemical reagents; alternatively, 2DE is combined with ex vivo experiments which are able to push the conditions that increase the PTM under study. Protein oxidative modifications, mainly, have been investigated using this approach, in AD and other NDs [ 43 ].…”

Section: Proteomics To Study the Pathobiology Of Neurodegenerative Di...mentioning

confidence: 99%

Current Insights on Neurodegeneration by the Italian Proteomics Community

2022

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The growing number of patients affected by neurodegenerative disorders represents a huge problem for healthcare systems, human society, and economics. In this context, omics strategies are crucial for the identification of molecular factors involved in disease pathobiology, and for the discovery of biomarkers that allow early diagnosis, patients’ stratification, and treatment response prediction. The integration of different omics data is a required step towards the goal of personalized medicine. The Italian proteomics community is actively developing and applying proteomics approaches to the study of neurodegenerative disorders; moreover, it is leading the mitochondria-focused initiative of the Human Proteome Project, which is particularly important given the central role of mitochondrial impairment in neurodegeneration. Here, we describe how Italian research groups in proteomics have contributed to the knowledge of many neurodegenerative diseases, through the elucidation of the pathobiology of these disorders, and through the discovery of disease biomarkers. In particular, we focus on the central role of post-translational modifications analysis, the implementation of network-based approaches in functional proteomics, the integration of different omics in a systems biology view, and the development of novel platforms for biomarker discovery for the high-throughput quantification of thousands of proteins at a time.

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Comparative Proteomics for the Evaluation of Protein Expression and Modifications in Neurodegenerative Diseases

Cited by 4 publications

References 137 publications

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications

Obscurin and Clusterin Elevation in Serum of Acute Myocardial Infarction Patients

Current Insights on Neurodegeneration by the Italian Proteomics Community

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