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A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases

Publication Type : Journal Article

Thematic Areas : Nanosciences and Molecular Medicine

Publisher : Molecular and Cellular Proteomics

Source : Molecular and Cellular Proteomics, Volume 10, Number 6 (2011)

Url :

Keywords : adult, aged, alpha crystallin, article, aspartate aminotransferase, beta crystallin, biological marker, biotinylation, brain homogenate, brain protein, cerebrospinal fluid analysis, clinical article, cofilin, collapsin response mediator protein 2, controlled study, cyclophilin A, down regulation, energy metabolism, enolase, female, gene expression, human, human tissue, immunohistochemistry, male, matrix assisted laser desorption ionization time of flight mass spectrometry, mitochondrial respiration, multiple sclerosis, myelin, nerve fiber membrane, nucleotide sequence, priority journal, protein 14 3 3, protein analysis, protein phosphorylation, protein targeting, proteomics, two dimensional gel electrophoresis, ubiquitin thiolesterase

Campus : Kochi

School : Center for Nanosciences

Center : Amrita Center for Nanosciences and Molecular Medicine Move, Nanosciences

Department : Nanosciences and Molecular Medicine

Year : 2011

Abstract : Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as αβ crystallin, enolase, and 14-3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases.

Cite this Research Publication : Krishnakumar N. Menon, Steer, D. L., Short, M., Petratos, S., Smith, I., and Bernard, C. C. A., “A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases”, Molecular and Cellular Proteomics, vol. 10, 2011.

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