Proteomics in Diagnostic Neuropathology
In the "postgenome" era, attention has turned to the proteome as a source of complementary diagnostic and prognostic information. Recent advances in imaging mass spectrometry (IMS) uses matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) to acquire up to 1,000 individual protein signals within the molecular weight range of 2,000 to over 100,000 in specific areas of tissue sections. The systematic investigation of these sections permits creation of specific molecular weight images (ion density maps) for each signal detected. Analysis of these images can reveal a collection of unique protein changes, or a "protein signature", of diagnostic and prognostic value. These signatures may also afford assessment of disease progression and tissue response to treatments. Combined with histology and molecular genetic analyses, new proteomic techniques should refine subclassifications and provide defining information about the pathogenesis of many central and peripheral nervous system diseases.
Available from: Robert J Unwin
- "However, although analysis of renal tissue requires a more invasive biopsy, the subset of proteins that can be extracted from renal tissue has different physico-chemical properties from those in urine, and proteomic analysis can provide valuable complementary data. Some examples are given in Table 2, including recent applications of MALDI-MS imaging technology for investigating the distribution of proteins within biological systems by direct analysis of thin sections cut from fresh frozen tissue samples      . Again, as with urinary proteomics, most of these reports are technical and descriptive and do not yet shed any light on the underlying mechanisms of renal injury or disease; although they do provide potential clues and important reference data for future comparisons. "
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ABSTRACT: The increasing application of proteomic methods to biomedical research is providing us with important new information; it holds particular promise in advancing basic and clinical renal research, but whether proteomics can ever become a routine diagnostic tool in nephrology is still uncertain. Currently, proteomic techniques are used by many groups in the search for “biomarkers” of disease, especially kidney disease, because of the ready availability of urine as an “end-product” of renal function. However, the question as to whether any disease-specific biomarkers exist or can be identified by proteomics is also uncertain. A growing application of proteomics in biomedical research is to understand the mechanism(s) of disease. This brief review is selective; in it we consider examples of proteomic studies of human urine for biomarkers, others that have explored renal physiology, and still others that have begun to probe the proteome of organelles. No single approach is sufficiently comprehensive, and the pooled application of proteomics to renal research will undoubtedly improve our understanding of renal function and enable us to explore in more detail subcellular structures, and to characterize cellular processes at the molecular level. When combined with other techniques in renal research, proteomics, and related analytical methods could prove indispensable in modeling renal function, and perhaps also in diagnosis and management of renal disease.
Available from: Travis Dunckley
- "Due to the fact that the energy of each cation is the same, acceleration is proportional to ion mass. Data is constructed as ion density maps by plotting mass/charge signal intensities over the sample area analyzed (Johnson et al. 2006). Overall, this method allows for high-throughput quantification of global protein expression in thin, heterogeneous tissue samples and is therefore an efficient tool in the search for neurological disease biomarkers. "
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ABSTRACT: Technology for high-throughout scanning of the human genome and its encoded proteins have rapidly developed to allow systematic analyses of human disease. Application of these technologies is becoming an increasingly effective approach for identifying the biological basis of genetically complex neurological diseases. This review will highlight significant findings resulting from the use of a multitude of genomic and proteomic technologies toward biomarker discovery in neurological disorders. Though substantial discoveries have been made, there is clearly significant promise and potential remaining to be fully realized through increasing use of and further development of -omic technologies.
Available from: Jonathan Sweedler
- "Any excess stain can be removed by submerging the tissue in ethanol, which as mentioned previously, also serves to fix proteins (Chaurand et al. 2004). Combining MALDI MSI with histological examination has aided in the identification of several novel biomarkers in human brain tumors (Johnson et al. 2006) and breast cancer (Chaurand et al. 2006). "
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ABSTRACT: Techniques that map the distribution of compounds in biological tissues can be invaluable in addressing a number of critical questions in biology and medicine. One of the newer methods, mass spectrometric imaging, has enabled investigation of spatial localization for a variety of compounds ranging from atomics to proteins. The ability of mass spectrometry to detect and differentiate a large number of unlabeled compounds makes the approach amenable to the study of complex biological tissues. This chapter focuses on recent advances in the instrumentation and sample preparation protocols that make mass spectrometric imaging of biological samples possible, including strategies for both tissue and single-cell imaging using the following mass spectrometric ionization methods: matrix-assisted laser desorption/ionization, secondary ion, electrospray, and desorption electrospray.
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