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Focused proteomics in post-mortem human spinal cord
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 Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Analytical Chemistry.
2006 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 5, no 9, p. 2364-2371Article in journal (Refereed) Published
Abstract [en]

With a highly sensitive electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) system, proteins were identified in minimal amounts of spinal cord from patients with the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and compared to proteins in spinal cord from control subjects. The results show 18 versus 16 significantly identified ( p < 0.05) proteins, respectively, all known to be found in the central nervous system. The most abundant protein in both groups was the glial fibrillary acidic protein, GFAP. Other proteins were, for example, hemoglobin alpha- and, chain, myelin basic protein, thioredoxin, R enolase, and cholin acetyltransferase. This study also includes the technique of laser microdissection in combination with pressure catapulting (LMPC) for the dissection of samples and specific neurons. Furthermore, complementary experiments with nanoLC-matrix assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF MS) confirmed the results of the ESI-FTICR MS screening and provided additional results of further identified proteins.

Place, publisher, year, edition, pages
2006. Vol. 5, no 9, p. 2364-2371
Keywords [en]
proteomics, electrospray ionization - Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS), matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-TOF-MS), neurodegeneration, amyotrophic lateral sclerosis, spinal cord, laser microdissection with pressure catapulting (LMPC)
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-82961DOI: 10.1021/pr060237fISI: 000240200700033PubMedID: 16944948OAI: oai:DiVA.org:uu-82961DiVA, id: diva2:110868
Available from: 2006-10-25 Created: 2006-10-25 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Cerebrum Illuminans: Mass Spectrometric Analysis of Protein and Peptide Dynamics in Neurological Diseases
Open this publication in new window or tab >>Cerebrum Illuminans: Mass Spectrometric Analysis of Protein and Peptide Dynamics in Neurological Diseases
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The human brain (lat. cerebrum) is the most complex and heterogeneous organ in the human body. It is involved in a great number of body functions like movement, touch sensing, vision, hearing, smelling, hormone regulation and many more. In no other organ, the molecular communication mechanisms between different cells are so poorly understood. Due to the extensive diversity of processes that are controlled by the brain, diseases and injuries of the nervous system affect the human body significantly. Because of the immense complexity of the brain, the molecular mechanisms underlying the pathology of the diseases remain largely unknown.

Hence, there is an urgent need for the development of new analytical strategies in order to investigate these conditions on a molecular level. Here, a central focus lies in the study of protein and peptide expression profiles, which can provide an insight in ongoing molecular mechanisms underlying the pathophysiology of the diseases. A powerful approach for studying proteins and peptide dynamics is mass spectrometry based proteomics, which is defined as the comprehensive study of all proteins expressed in a biological matrix at a certain point of time.

The central objective of this thesis was to develop and employ different mass spectrometric techniques to study protein and peptide dynamics in the central nervous system in different neurological diseases. The individual studies comprise different aspects of proteome research. The first two studies included clinical proteomic applications for investigating protein dynamics in traumatic brain injury and amyotrophic lateral sclerosis. A further study was focused on method development for MS analysis of intact neural cells. The final three projects described in this thesis comprised MS based protein and peptide imaging in brain and spinal cord tissue samples. Here, the aim was to elucidate topological changes in protein expression in ALS as well as neuropeptide alterations in distinct brain structures in L-DOPA induced dyskinesia (LID) in Parkinson’s disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. p. 87
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 783
Keywords
mass spectrometry, central nervous system, neurological disease, proteomics, MALDI imaging
National Category
Analytical Chemistry
Research subject
Chemistry with specialization in Analytical Chemistry
Identifiers
urn:nbn:se:uu:diva-132908 (URN)978-91-554-7937-4 (ISBN)
Public defence
2010-12-10, B41, Uppsala Biomedical Center, Husargatan 3, Uppsala, 10:15 (English)
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Note
Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 713Available from: 2010-11-19 Created: 2010-10-28 Last updated: 2022-01-28

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Ekegren, TittiHanrieder, JörgAquilonius, Sten-MagnusBergquist, Jonas

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