Neuroproteomics in neurotrauma

Center of Neuroproteomics and Biomarkers Research, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Mass Spectrometry Reviews (Impact Factor: 7.71). 05/2006; 25(3):380-408. DOI: 10.1002/mas.20073
Source: PubMed


Neurotrauma in the form of traumatic brain injury (TBI) afflicts more Americans annually than Alzheimer's and Parkinson's disease combined, yet few researchers have used neuroproteomics to investigate the underlying complex molecular events that exacerbate TBI. Discussed in this review is the methodology needed to explore the neurotrauma proteome-from the types of samples used to the mass spectrometry identification and quantification techniques available. This neuroproteomics survey presents a framework for large-scale protein research in neurotrauma, as applied for immediate TBI biomarker discovery and the far-reaching systems biology understanding of how the brain responds to trauma. Ultimately, knowledge attained through neuroproteomics could lead to clinical diagnostics and therapeutics to lessen the burden of neurotrauma on society.

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Available from: William Haskins
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    • "It was no different with neurological conditions such as TBI, Alzheimer’s disease, and stroke. Neuroproteomics (Choudhary and Grant, 2004), a field under the proteomics umbrella, has zeroed in these disorders, extracting insights into the dynamics and interactions of proteins in these disease states (Ottens et al., 2006, 2010; Bayes and Grant, 2009; Alzate, 2010; Shoemaker et al., 2012). "
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    ABSTRACT: Traumatic brain injury (TBI) is a major medical crisis without any FDA-approved pharmacological therapies that have been demonstrated to improve functional outcomes. It has been argued that discovery of disease-relevant biomarkers might help to guide successful clinical trials for TBI. Major advances in mass spectrometry (MS) have revolutionized the field of proteomic biomarker discovery and facilitated the identification of several candidate markers that are being further evaluated for their efficacy as TBI biomarkers. However, several hurdles have to be overcome even during the discovery phase which is only the first step in the long process of biomarker development. The high-throughput nature of MS-based proteomic experiments generates a massive amount of mass spectral data presenting great challenges in downstream interpretation. Currently, different bioinformatics platforms are available for functional analysis and data mining of MS-generated proteomic data. These tools provide a way to convert data sets to biologically interpretable results and functional outcomes. A strategy that has promise in advancing biomarker development involves the triad of proteomics, bioinformatics, and systems biology. In this review, a brief overview of how bioinformatics and systems biology tools analyze, transform, and interpret complex MS datasets into biologically relevant results is discussed. In addition, challenges and limitations of proteomics, bioinformatics, and systems biology in TBI biomarker discovery are presented. A brief survey of researches that utilized these three overlapping disciplines in TBI biomarker discovery is also presented. Finally, examples of TBI biomarkers and their applications are discussed.
    Full-text · Article · May 2013 · Frontiers in Neurology
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    • "Since the overall prognosis in the majority of mTBI cases is positive, this strengthens the hypothesis that there must be naturally occurring, active homeostatic and restorative mechanisms at work during post-traumatic recovery (Wager- Smith and Markou 2010). Ottens et al. (2006) discuss the 'neuroproteomics of injury' which broadly implicates proteins and their role in cellular structure and pathology following trauma as well as their role in recovery and repair. As has been shown in this review there are multiple neuropathological events following injury where cellular function may be disrupted, including the eventual onset of programmed cell death. "
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    ABSTRACT: Neuroimaging identified abnormalities associated with traumatic brain injury (TBI) are but gross indicators that reflect underlying trauma-induced neuropathology at the cellular level. This review examines how cellular pathology relates to neuroimaging findings with the objective of more closely relating how neuroimaging findings reveal underlying neuropathology. Throughout this review an attempt will be made to relate what is directly known from post-mortem microscopic and gross anatomical studies of TBI of all severity levels to the types of lesions and abnormalities observed in contemporary neuroimaging of TBI, with an emphasis on mild traumatic brain injury (mTBI). However, it is impossible to discuss the neuropathology of mTBI without discussing what occurs with more severe injury and viewing pathological changes on some continuum from the mildest to the most severe. Historical milestones in understanding the neuropathology of mTBI are reviewed along with implications for future directions in the examination of neuroimaging and neuropathological correlates of TBI.
    Full-text · Article · Mar 2012 · Brain Imaging and Behavior
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    • "Lymphocytes were challenged as neural probes for AD-related metabolic changes in the brain (Gladkevich et al., 2004). The results of early neuroproteomic and proteomics-driven progress in neurodegeneration research have been reviewed by several authors (Ottens et al., 2006; Johnson et al., 2005; Fountoulakis and Kossida, 2006). The methods of clinical, structural and functional proteomics have been summarized from a mass spectrometric point of view by Drabik et al. (2007). "
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    ABSTRACT: Alzheimer's disease (AD) is a protein misfolding-based rapid cognitive impairment in the aging brain. Because of its very widespread molecular background, AD has been approached using genomic and proteomic methods and has accumulated a large body of data during the last 15 years. In this review, we summarize the systems biology data on AD and pay particular attention to the proteomic changes in AD. Applying a systems biology model of the synapse, we attempt to integrate protein changes and provide an explanation of why seemingly diverse molecular changes result in memory impairment. We also summarize the present state of cerebrospinal fluid (CSF) and blood biomarker studies for the diagnosis of AD as well as the results of proteomic studies in tissue cultures and animal models. Finally, we give a systems biology model of AD explaining how AD can develop in an individual manner in each particular subject but always results in a rapidly developing dementia and memory impairment.
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