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Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: Exemplified in amyotrophic lateral sclerosis biomarker discovery research
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
2008 (English)In: Journal of Mass Spectrometry, ISSN 1076-5174, E-ISSN 1096-9888, Vol. 43, no 5, 559-571 p.Article in journal (Refereed) Published
Abstract [en]

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 neuro degenerative 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).

Place, publisher, year, edition, pages
2008. Vol. 43, no 5, 559-571 p.
Keyword [en]
Biomarker, Clinical proteomics, Amyotrophic lateral sclerosis, Neurodegeneration, FTICR-MS, MALDI-TOF-TOF MS, Cerebrospinal fluid, Nervous tissue
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16225DOI: 10.1002/jms.1409ISI: 000256451700001OAI: oai:DiVA.org:uu-16225DiVA: diva2:43996
Available from: 2008-05-13 Created: 2008-05-13 Last updated: 2017-12-08Bibliographically approved

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Ekegren, TittiHanrieder, JörgBergquist, Jonas

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