Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia A-T Patients Using a LC-MS-Based Label-Free Protein Quantification TechnologyReport as inadecuate




Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia A-T Patients Using a LC-MS-Based Label-Free Protein Quantification Technology - Download this document for free, or read online. Document in PDF available to download.

International Journal of ProteomicsVolume 2011 2011, Article ID 578903, 13 pages

Research Article

Department Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Dr., MS 4053, Indianapolis, IN 46202, USA

Division of Pediatric Allergy and Immunology, Departments of Pediatrics, Medicine, and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

Division of Pediatric Neurology, Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA

Research Department, A-T Children-s Project, Coconut Creek, FL 33073, USA

Received 24 January 2011; Accepted 18 March 2011

Academic Editor: Visith Thongboonkerd

Copyright © 2011 Monika Dzieciatkowska et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cerebrospinal fluid CSF has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein ATM, a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanisms underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC-MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers.





Author: Monika Dzieciatkowska, Guihong Qi, Jinsam You, Kerry G. Bemis, Heather Sahm, Howard M. Lederman, Thomas O. Crawford, Lawren

Source: https://www.hindawi.com/



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