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Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: exemplified in amyotrophic lateral sclerosis biomarker discovery research.

Review article
Authors Titti Ekegren
Jörg Hanrieder
Jonas Bergquist
Published in Journal of mass spectrometry : JMS
Volume 43
Issue 5
Pages 559-71
ISSN 1076-5174
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 559-71
Language en
Links dx.doi.org/10.1002/jms.1409
Keywords Amyotrophic Lateral Sclerosis, diagnosis, metabolism, Biomarkers, analysis, Brain, metabolism, Humans, Mass Spectrometry, trends, Nerve Tissue Proteins, analysis, Neurosciences, trends, Proteome, analysis, Proteomics, trends
Subject categories Neurology, Clinical chemistry, Neurobiology, Neurochemistry, Analytical Chemistry, Biological Sciences

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).

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