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Clinical perspectives of high‐resolution mass spectrometry–based proteomics in neuroscience—Exemplified in amyotrophic lateral sclerosis biomarker discovery research
Author(s) -
Ekegren Titti,
Hanrieder Jörg,
Bergquist Jonas
Publication year - 2008
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1409
Subject(s) - biomarker discovery , proteomics , chemistry , biomarker , mass spectrometry , fourier transform ion cyclotron resonance , top down proteomics , amyotrophic lateral sclerosis , tandem mass spectrometry , computational biology , selected reaction monitoring , chromatography , disease , medicine , pathology , biochemistry , biology , gene
Abstract Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high‐throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel‐based approaches as well as chromatographic techniques for multi‐dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS‐based clinical proteomics and biomarker discovery in the field of neurodegenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high‐resolution MS‐based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography‐Fourier transform ion cyclotron resonance mass spectrometry (LC‐FTICR‐MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro‐dissected motor neurons using FT‐ICR‐MS in conjunction with nanoflow LC coupled to matrix‐assisted laser desorption ionization time‐of‐flight tandem mass spectrometry (LC‐MALDI‐TOF‐TOF‐MS). Copyright © 2008 John Wiley & Sons, Ltd.