Abstract The Neuronal Ceroid Lipofuscinoses (NCL) are a group of fatal inherited neurodegenerative diseases in humans distinguished by a common clinical pathology, characterized by the accumulation of storage body material in cells and gross brain atrophy. In this study, metabolic changes in three NCL mouse models were examined looking for pathways correlated with neurodegeneration. Two mouse models; motor neuron degeneration (mnd) mouse and a variant model of late infantile NCL, termed the neuronal ceroid lipofuscinosis (nclf) mouse were investigated experimentally. Both models exhibit a characteristic accumulation of autofluorescent lipopigment in neuronal and non neuronal cells. The NMR profiles derived from extracts of the cortex and cerebellum from mnd and nclf mice were distinguished according to disease/wildtype status. In particular, a perturbation in glutamine and glutamate metabolism, and a decrease in γ-amino butyric acid (GABA) in the cerebellum and cortices of mnd (adolescent mice) and nclf mice relative to wildtype at all ages were detected. Our results were compared to the Cln3 mouse model of NCL. The metabolism of mnd mice resembled older (6 month) Cln3 mice, where the disease is relatively advanced, while the metabolism of nclf mice was more akin to younger (1-2 months) Cln3 mice, where the disease is in its early stages of progression. Overall, our results allowed the identification of metabolic traits common to all NCL subtypes for the three animal models.
Content Type Journal Article
Pages 1-10
DOI 10.1007/s10858-011-9491-7
Authors
Reza M. Salek, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
Michael R. Pears, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
Jonathan D. Cooper, Pediatric Storage Disorders Laboratory, Department of Neuroscience, Institute of Psychiatry, Kingâ??s College London, London, UK
Hannah M. Mitchison, Department of Paediatrics and Child Health, Royal Free and University College Medical School, London, UK
David A. Pearce, Department of Pediatrics, Sanford School of Medicine of the University of South Dakota, 2301 East 60th Street North, Sioux Falls, SD 57104-0589, USA
Russell J. Mortishire-Smith, Johnson & Johnson PR & D, Turnhoutsweg 30, 2340 Beerse, Belgium
Julian L. Griffin, Department of Biochemistry and the Cambridge Systems Biology Centre, University of Cambridge, 80 Tennis Court Road, Cambridge, CB2 1GA, UK
A Large-scale Comparison of Computational Models on the Residue Flexibility for NMR-derived Proteinss.
A Large-scale Comparison of Computational Models on the Residue Flexibility for NMR-derived Proteinss.
A Large-scale Comparison of Computational Models on the Residue Flexibility for NMR-derived Proteinss.
Protein Pept Lett. 2011 Sep 20;
Authors: Zhang H, Shi H, Hanlon M
Abstract
As an alternative to X-ray crystallography, nuclear magnetic resonance (NMR) has also emerged as the method of choice for studying both protein structure and dynamics in solution. However, little work using computational models such as Gaussian network model...
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Use of optimized 1D TOCSY NMR for improved quantitation and metabolomic analysis of biofluids
Use of optimized 1D TOCSY NMR for improved quantitation and metabolomic analysis of biofluids
Abstract One dimensional selective TOCSY experiments have been shown to be advantageous in providing improved data inputs for principle component analysis (PCA) (Sandusky and Raftery 2005a, b). Better subpopulation cluster resolution in the observed scores plots results from the ability to isolate metabolite signals of interest via the TOCSY based filtering approach. This report reexamines the quantitative aspects of this approach, first by optimizing the 1D TOCSY experiment as it relates to...
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03-13-2011 05:24 AM
Towards automatic metabolomic profiling of high-resolution one-dimensional proton NMR spectra
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Abstract Nuclear magnetic resonance (NMR) and Mass Spectroscopy (MS) are the two most common spectroscopic analytical techniques employed in metabolomics. The large spectral datasets generated by NMR and MS are often analyzed using data reduction techniques like Principal Component Analysis (PCA). Although rapid, these methods are susceptible to solvent and matrix effects, high rates of false positives, lack of reproducibility and limited data transferability from one platform to the next....
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03-03-2011 02:06 AM
Descriptive Review of Current NMR-Based Metabolomic Data Analysis Packages
Descriptive Review of Current NMR-Based Metabolomic Data Analysis Packages
Publication year: 2011
Source: Progress in Nuclear Magnetic Resonance Spectroscopy, In Press, Accepted Manuscript, Available online 21 February 2011</br>
Jose L., Izquierdo-García , Palmira, Villa , Angelos, Kyriazis , Laura del, Puerto-Nevado , Sandra, Pérez-Rial , ...</br>
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02-22-2011 11:00 AM
[NMR paper] High-resolution magic angle spinning NMR of the neuronal tau protein integrated in Alzheimer's-like paired helical fragments.
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HRMAS NMR of tau paired helical fragments assembled with heparin show an intensity decrease for those amino acids that are incorporated into the rigid core...
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[NMR paper] Accepting its random coil nature allows a partial NMR assignment of the neuronal Tau
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A combined strategy to obtain a partial NMR assignment of the neuronal Tau protein is presented. Confronted with the extreme spectral degeneracy that the spectrum of this 441 amino acid long unstructured protein presents, we have...
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11-24-2010 10:03 PM
[NMR paper] Vitamin C metabolomic mapping in the lens with 6-deoxy-6-fluoro-ascorbic acid and hig
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Authors: Satake M, Dmochowska B, Nishikawa Y, Madaj J, Xue J, Guo Z, Reddy DV, Rinaldi PL, Monnier VM
PURPOSE: Metabolomics, or metabolic profiling, is an emerging discipline geared to providing information on a large number of metabolites,...
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11-24-2010 09:01 PM
NMR Metabolomic Profiling Reveals New Roles of SUMOylation in DNA Damage Response.
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http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles NMR Metabolomic Profiling Reveals New Roles of SUMOylation in DNA Damage Response.
J Proteome Res. 2010 Aug 9;
Authors: Cano KE, Li YJ, Chen Y
Post-translational modifications by the Small Ubiquitin-like Modifier (SUMO) family of proteins have been established as critical events in the cellular response to a wide range of DNA damaging reagents and radiation;...
A metabolomic comparison of mouse models of the Neuronal Ceroid Lipofuscinoses
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