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Firas Kobeissy - One of the best experts on this subject based on the ideXlab platform.

  • The Emerging Role of Proteomics in Precision Medicine: Applications in Neurodegenerative Diseases and Neurotrauma.
    Advances in Experimental Medicine and Biology, 2017
    Co-Authors: Rana Alaaeddine, Mira Fayad, Eliana Nehme, Hisham F. Bahmad, Firas Kobeissy
    Abstract:

    Inter-individual variability in response to pharmacotherapy has provoked a higher demand to personalize medical decisions. As the field of pharmacogenomics has served to translate personalized medicine from concept to practice, the contribution of the “omics” disciplines to the era of precision medicine seems to be vital in improving therapeutic outcomes. Although we have observed significant advances in the field of genomics towards personalized medicine, the field of proteomics-with all its capabilities- is still in its infancy towards the area of personalized precision medicine. Neurodegenerative diseases and neurotrauma are among the areas where the implementation of Neuroproteomics approaches has enabled neuroscientists to broaden their understanding of neural disease mechanisms and characteristics. It has been shown that the influence of epigenetics, genetics and environmental factors were among the recognized factors contributing to the diverse presentation of a single disease as well as its treatment establishing the factor–disease interaction. Thus, management of these variable single disease presentation/outcome necessitated the need for factoring the influence of epigenetics, genetics, epigenetics, and other factors on disease progression to create a custom treatment plan unique to each individual. In fact, Neuroproteomics with its high ability to decipher protein alterations along with their post translational modifications (PTMs) can be an ideal tool for personalized medicine goals including: discovery of molecular mechanisms underlying disease pathobiology, development of novel diagnostics, enhancement of pharmacological neurotherapeutic approaches and finally, providing a “proteome identity” for patients with certain disorders and diseases. So far, Neuroproteomics approaches have excelled in the areas of biomarker discovery arena where several diagnostic, prognostic and injury markers have been identified with a direct impact on the neurodegenerative diseases and neurotrauma. However, other applications in proteomics such as “individual” proteome sequencing with its signature PTMs, have not been fully investigated as compared to the achievements in the genomics discipline This infers that proteomics research work has promising potential, yet to be discovered, in the precision medicine and comprises a major component of the personalized medicine infrastructure as it allows individual characterization of disease at the protein level. To conclude, the field of proteomics-based personalized medicine is still in its infancy compared to genomics field due to several technical and instrumentation-based obstacles; however, we anticipate to have this initiative leading in the coming future. This chapter will discuss briefly how Neuroproteomics can impact personalized medicine in the fields of neurodegenerative disorders particularly in Alzheimer’s disease and brain injury.

  • Neuroproteomics Studies: Challenges and Updates.
    Methods of Molecular Biology, 2017
    Co-Authors: Naify Ramadan, Hussein Ghazale, Mohammad El-sayyad, Mohamad El-haress, Firas Kobeissy
    Abstract:

    The Human Genome Project in 2003 has resulted in the complete sequence of ~99% of the human genome paving the road for the Human Proteome Project (HPP) assessing the full characterization of the translated protein map of the 20,300 protein-coding genes. Consequently, the emerging of the proteomics field has successfully been adopted as the method of choice for the proteome characterization. Proteomics is a term that is used to encompass multidisciplinary approaches combining different technologies that aim to study the entire spectrum of protein changes at a specific physiological condition. Proteomics research has shown excellent outcomes in different fields, among which is neuroscience; however, the complexity of the nervous systems necessitated the genesis of a new subdiscipline of proteomics termed as "Neuroproteomics." Neuroproteomics studies involve assessing the quantitative and qualitative aspects of nervous system components encompassing global dynamic events underlying various brain-related disorders ranging from neuropsychiatric disorders, degenerative disorders, mental illness, and most importantly brain-specific neurotrauma-related injuries. In this introductory chapter, we will provide a brief historical perspective on the field of Neuroproteomics. In doing so, we will highlight on the recent applications of Neuroproteomics in the areas of neurotrauma, an area that has benefitted from Neuroproteomics in terms of biomarker research, spatiotemporal injury mechanism, and its use to translate its findings from experimental settings to human translational applications. Importantly, this chapter will include some recommendation to the general studies in the area of Neuroproteomics and the need to move from this field from being a descriptive, hypothesis-free approach to being an independent mature scientific discipline.

  • Deciphering the Role of Emx1 in Neurogenesis: A Neuroproteomics Approach
    Frontiers in Molecular Neuroscience, 2016
    Co-Authors: Firas Kobeissy, Katharina Hansen, Melanie Neumann, Kunlin Jin, Jialing Liu
    Abstract:

    Emx1 has long been implicated in embryonic brain development. Previously we found that mice null of Emx1 gene had smaller dentate gyri and reduced neurogenesis, although the molecular mechanisms underlying this defect was not well understood. To decipher the role of Emx1 gene in neural regeneration and the timing of its involvement, we determine the frequency of neural stem cells (NSCs) in embryonic and adult forebrains of Emx1 wild type (WT) and knock out (KO) mice in the neurosphere assay. Emx1 gene deletion reduced the frequency and self-renewal capacity of neural stem cells (NSCs) of the embryonic brain but did not affect neuronal or glial differentiation. Emx1 KO NSCs also exhibited a reduced migratory capacity in response to serum or vascular endothelial growth factor (VEGF) in the Boyden chamber migration assay compared to their WT counterparts. A thorough comparison between NSC lysates from Emx1 WT and KO mice utilizing 2D-PAGE coupled with tandem mass spectrometry revealed 38 proteins differentially expressed between genotypes, including the F-actin depolymerization factor Cofilin. A global systems biology and cluster analysis identified several potential mechanisms and cellular pathways implicated in altered neurogenesis, all involving Cofilin1. Protein interaction network maps with functional enrichment analysis further indicated that the differentially expressed proteins participated in neural-specific functions including brain development, axonal guidance, synaptic transmission, neurogenesis and hippocampal morphology, with VEGF as the upstream regulator intertwined with Cofilin1 and Emx1. Functional validation analysis indicated that apart from the overall reduced level of phosphorylated Cofilin1 (p-Cofilin1) in the Emx1 KO NSCs compared to WT NSCs as demonstrated in the western blot analysis, VEGF was able to induce more Cofilin1 phosphorylation and FLK expression only in the latter. Our results suggest that a defect in Cofilin1 phosphorylation induced by VEGF or other growth factors might contribute to the reduced neurogenesis in the Emx1 null mice during brain development.

  • Application of Systems Biology to Neuroproteomics: The Path to Enhanced Theranostics in Traumatic Brain Injury.
    Methods of Molecular Biology, 2016
    Co-Authors: Zaynab Jaber, Hisham F. Bahmad, Patrick Aouad, Mohamad Al Medawar, Hussein Abou-abbass, Firas Kobeissy
    Abstract:

    The application of systems biology tools in analyzing heterogeneous data from multiple sources has become a necessity, especially in biomarker discovery. Such tools were developed with several approaches to address different types of research questions and hypotheses. In the field of neurotrauma and traumatic brain injury (TBI), three distinct approaches have been used so far as systems biology tools, namely functional group categorization, pathway analysis, and protein-protein interaction (PPI) networks. The databases allow for query of the system to identify candidate targets which can be further studied to elucidate potential downstream biomarkers indicative of disease progression, severity, and improvement. The various systems biology tools, databases, and strategies that can be implemented on available TBI data in neuroproteomic studies are discussed in this chapter.

  • Recent updates on drug abuse analyzed by Neuroproteomics studies: Cocaine, Methamphetamine and MDMA
    Translational Proteomics, 2014
    Co-Authors: Firas Kobeissy, Kevin K. W. Wang, Zhiqun Zhang, Tarek H. Mouhieddine, Amaly Nokkari, Muhieddine M. Itani, Mohammed Mouhieddine, Rui Zhu, Mark S. Gold, Yehia Mechref
    Abstract:

    Abstract Currently, drug abuse and addiction represent a global public health concern with about 13.6 million people using illicit drugs in the USA alone. Substance abuse intervenes in normal brain functioning, causing alterations in memory, behavior and neuronal physiology. Although many studies have been conducted to elucidate the mode of action of different drugs, the heterogeneous modes of drug intake led to a complicated profile of drug-induced brain changes involving neurotoxicity and addiction. Given the complex interplay of genes and proteins in mediating these effects, Neuroproteomics analysis has been considered among the methods of choice to complement what has already been discovered and to create targeted therapies. In this review, we will focus on three drugs, namely cocaine, methamphetamine (METH) and 3,4-methylenedioxy-N-methylamphetamine (MDMA). In the context of Neuroproteomics, these drugs have been extensively studied by utilizing different experimental models, including primate and non-primate animals along with postmortem human samples. Even though there are many variations in the results, these drugs were shown to employ common pathways in eliciting their effects. Neuroproteomics analysis of these drugs has led to the identification of differentially expressed proteins involved in metabolism, oxidative stress, cell signaling, cytoskeleton, cell death and synaptic plasticity. Finally, this work will discuss recent findings from our laboratory by looking at a model of chronic methamphetamine abuse and its effect on different brain regions.

Kevin K. W. Wang - One of the best experts on this subject based on the ideXlab platform.

  • Recent updates on drug abuse analyzed by Neuroproteomics studies: Cocaine, Methamphetamine and MDMA
    Translational Proteomics, 2014
    Co-Authors: Firas Kobeissy, Kevin K. W. Wang, Zhiqun Zhang, Tarek H. Mouhieddine, Amaly Nokkari, Muhieddine M. Itani, Mohammed Mouhieddine, Rui Zhu, Mark S. Gold, Yehia Mechref
    Abstract:

    Abstract Currently, drug abuse and addiction represent a global public health concern with about 13.6 million people using illicit drugs in the USA alone. Substance abuse intervenes in normal brain functioning, causing alterations in memory, behavior and neuronal physiology. Although many studies have been conducted to elucidate the mode of action of different drugs, the heterogeneous modes of drug intake led to a complicated profile of drug-induced brain changes involving neurotoxicity and addiction. Given the complex interplay of genes and proteins in mediating these effects, Neuroproteomics analysis has been considered among the methods of choice to complement what has already been discovered and to create targeted therapies. In this review, we will focus on three drugs, namely cocaine, methamphetamine (METH) and 3,4-methylenedioxy-N-methylamphetamine (MDMA). In the context of Neuroproteomics, these drugs have been extensively studied by utilizing different experimental models, including primate and non-primate animals along with postmortem human samples. Even though there are many variations in the results, these drugs were shown to employ common pathways in eliciting their effects. Neuroproteomics analysis of these drugs has led to the identification of differentially expressed proteins involved in metabolism, oxidative stress, cell signaling, cytoskeleton, cell death and synaptic plasticity. Finally, this work will discuss recent findings from our laboratory by looking at a model of chronic methamphetamine abuse and its effect on different brain regions.

  • Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma.
    Electrophoresis, 2012
    Co-Authors: Mohamad Raad, Kevin K. W. Wang, Zhiqun Zhang, Stefania Mondello, Tala El Tal, Rukhsana Gul, Rose-mary Boustany, Joy Guingab, Firas Kobeissy
    Abstract:

    Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of Neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how Neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma.

  • Data Mining Strategies Applied in Brain Injury Models
    Data Mining for Biomarker Discovery, 2012
    Co-Authors: Stefania Mondello, Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Isaac Fingers, Kevin K. W. Wang
    Abstract:

    Traumatic brain injury or traumatic head injury is characterized as a direct physical impact or trauma to the head, causing brain injury. It represents a major national health problem without a US Food and Drug Administration-approved therapy. The application of Neuroproteomics/neurogenomics has revolutionized the characterization of protein/gene dynamics, leading to a greater understanding of post-injury biochemistry. Neuroproteomics and Neurogenomics fields have undertaken major advances in the area of neurotrauma research focusing on biomarker identification. Several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers utilizing these “omics approaches”. The identification of these differentially expressed candidate markers using these techniques is proving to be only the first step in the biomarker development process. However, to translate these findings into the clinic, data-driven development cycle incorporating data-mining steps for discovery, qualification, verification, and clinical validation is needed. Data mining steps extend beyond the collected data level into an integrated scheme of animal modeling, instrumentation, and functional data analysis. In this chapter, we provide an introductory review of data-mining/systems biology coupled approaches that have been applied to biomarker discovery and clinical validation; in addition, the need for strengthening the integral roles of these disciplines in establishing a comprehensive understanding of specific brain disorder and biomarker identification in general.

  • Leveraging biomarker platforms and systems biology for rehabilomics and biologics effectiveness research.
    Pm&r, 2011
    Co-Authors: Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Joy Guingab-cagmat, Razafsha, Laura E. O'steen, Wen Ta Chiu, Kevin K. W. Wang
    Abstract:

    Abstract Although traumatic brain injury (TBI) remains a major health problem, with approximately 2 million incidents occurring annually in the United States, no therapeutic agents to treat TBI have been approved by the Food and Drug Administration despite several clinical trials. It is estimated that 3.5 million Americans now have a lifelong condition that might be termed "chronic traumatic brain injury disease.'' Some health care providers categorize TBI as an "event" for which patients require brief periods of rehabilitation with no further treatment. On the contrary, TBI should be seen as a chronic disease process that fits the World Health Organization definition as being a non-reversible pathologic condition requiring special rehabilitation training. Among the major obstacles that contribute to this type of misconception is the absence of brain injury–specific diagnostic biomarker(s) that can indicate and monitor the long-term health status of patients with TBI after use of conventional therapeutics and a rehabilitation process. It is of interest that recent advances in genomics, proteomics, and systems biology have enabled us to use these high throughput–based approaches in developing biomarkers and therapeutic targets in the area of TBI. One aim of this article is to provide an overview that evaluates the current status of TBI biomarker discovery using Neuroproteomics/systems biology techniques, along with their clinical utilization. In addition, we discuss the need for strengthening the role of biomarker-based Neuroproteomics/systems biology and its potential utility in the field of rehabilitation, which would lead to the establishment of rehabilomics studies, where biomarkers would indicate and predict the long-term efficacy and health status of patients with chronic TBI conditions.

  • Methods in drug abuse Neuroproteomics: methamphetamine psychoproteome.
    Methods of Molecular Biology, 2009
    Co-Authors: Firas Kobeissy, Shankar Sadasivan, Zhiqun Zhang, Mark S. Gold, Kevin K. W. Wang
    Abstract:

    Methamphetamine (METH) is recognized as one of the most abused psychostimulants in the USA. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying MDMA and METH-induced neurotoxic effects both in vivo and in vitro. Our substance abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. Altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. Proteins that were shown to be downregulated included collapsin response mediator protein-2 (CRMP-2), superoxide dismutase 1 (SOD 1), and phosphatidylethanolamine-binding protein-1 (PEBP-1). Proteins that were shown to be upregulated included authophagy-linked microtubule-associated protein light chain 3 (LC3), synapsin-1, and Parkinsonism-linked ubiquitin carboxy-terminal hydroxylase-L1 (UCH-L1). This differential protein expression highlights on the neurotoxic mechanism involved in METH exposure as well as to discover potential markers for METH-induced neurotoxicity. In this chapter, we describe the current protocols for the in vivo rat model of acute METH treatment (40 mg/kg) coupled with the description of the multistep separation platform applied. These methods and protocols are discussed in the paradigm of acute model of methamphetamine drug abuse and can be applied to other models of substance abuse such as to MDMA or cocaine.

Ronald L. Hayes - One of the best experts on this subject based on the ideXlab platform.

  • Data Mining Strategies Applied in Brain Injury Models
    Data Mining for Biomarker Discovery, 2012
    Co-Authors: Stefania Mondello, Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Isaac Fingers, Kevin K. W. Wang
    Abstract:

    Traumatic brain injury or traumatic head injury is characterized as a direct physical impact or trauma to the head, causing brain injury. It represents a major national health problem without a US Food and Drug Administration-approved therapy. The application of Neuroproteomics/neurogenomics has revolutionized the characterization of protein/gene dynamics, leading to a greater understanding of post-injury biochemistry. Neuroproteomics and Neurogenomics fields have undertaken major advances in the area of neurotrauma research focusing on biomarker identification. Several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers utilizing these “omics approaches”. The identification of these differentially expressed candidate markers using these techniques is proving to be only the first step in the biomarker development process. However, to translate these findings into the clinic, data-driven development cycle incorporating data-mining steps for discovery, qualification, verification, and clinical validation is needed. Data mining steps extend beyond the collected data level into an integrated scheme of animal modeling, instrumentation, and functional data analysis. In this chapter, we provide an introductory review of data-mining/systems biology coupled approaches that have been applied to biomarker discovery and clinical validation; in addition, the need for strengthening the integral roles of these disciplines in establishing a comprehensive understanding of specific brain disorder and biomarker identification in general.

  • Leveraging biomarker platforms and systems biology for rehabilomics and biologics effectiveness research.
    Pm&r, 2011
    Co-Authors: Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Joy Guingab-cagmat, Razafsha, Laura E. O'steen, Wen Ta Chiu, Kevin K. W. Wang
    Abstract:

    Abstract Although traumatic brain injury (TBI) remains a major health problem, with approximately 2 million incidents occurring annually in the United States, no therapeutic agents to treat TBI have been approved by the Food and Drug Administration despite several clinical trials. It is estimated that 3.5 million Americans now have a lifelong condition that might be termed "chronic traumatic brain injury disease.'' Some health care providers categorize TBI as an "event" for which patients require brief periods of rehabilitation with no further treatment. On the contrary, TBI should be seen as a chronic disease process that fits the World Health Organization definition as being a non-reversible pathologic condition requiring special rehabilitation training. Among the major obstacles that contribute to this type of misconception is the absence of brain injury–specific diagnostic biomarker(s) that can indicate and monitor the long-term health status of patients with TBI after use of conventional therapeutics and a rehabilitation process. It is of interest that recent advances in genomics, proteomics, and systems biology have enabled us to use these high throughput–based approaches in developing biomarkers and therapeutic targets in the area of TBI. One aim of this article is to provide an overview that evaluates the current status of TBI biomarker discovery using Neuroproteomics/systems biology techniques, along with their clinical utilization. In addition, we discuss the need for strengthening the role of biomarker-based Neuroproteomics/systems biology and its potential utility in the field of rehabilitation, which would lead to the establishment of rehabilomics studies, where biomarkers would indicate and predict the long-term efficacy and health status of patients with chronic TBI conditions.

  • Neuroproteomics: A Biochemical Means to Discriminate the Extent and Modality of Brain Injury
    Journal of Neurotrauma, 2010
    Co-Authors: Andrew K. Ottens, Ronald L. Hayes, Erin C. Golden, Changping Yao, Frank C. Tortella, Liliana Bustamante, Kang Kandy Wang, Jitendra R. Dave
    Abstract:

    Abstract Diagnosis and treatment of stroke and traumatic brain injury remain significant health care challenges to society. Patient care stands to benefit from an improved understanding of the interactive biochemistry underlying neurotrauma pathobiology. In this study, we assessed the power of Neuroproteomics to contrast biochemical responses following ischemic and traumatic brain injuries in the rat. A middle cerebral artery occlusion (MCAO) model was employed in groups of 30-min and 2-h focal neocortical ischemia with reperfusion. Neuroproteomes were assessed via tandem cation-anion exchange chromatography–gel electrophoresis, followed by reversed-phase liquid chromatography–tandem mass spectrometry. MCAO results were compared with those from a previous study of focal contusional brain injury employing the same methodology to characterize homologous neocortical tissues at 2 days post-injury. The 30-min MCAO neuroproteome depicted abridged energy production involving pentose phosphate, modulated synaptic...

  • Translation of neurological biomarkers to clinically relevant platforms.
    Methods of Molecular Biology, 2009
    Co-Authors: Ronald L. Hayes, Gillian Robinson, Uwe Müller, Kevin K. W. Wang
    Abstract:

    Summary Like proteomics more generally, Neuroproteomics has recently been linked to the discovery of biochemical markers of central nervous system (CNS) injury and disease. Although Neuroproteomics has enjoyed considerable success in discovery of candidate biomarkers, there are a number of challenges facing inves-tigators interested in developing clinically useful platforms to assess biomarkers for damage to the CNS. These challenges include intrinsic physiological complications such as the blood–brain barrier. Effective translation of biomarkers to clinical practice also requires development of entirely novel pathways and product development strategies. Drawing from lessons learned from applications of biomarkers to traumatic brain injury, this study outlines major elements of such a pathway. As with other indications, biomarkers can have three major areas of application: (1) drug development; (2) diagnosis and pr ognosis; (3) patient management. Translation of CNS biomarkers to practical clinical platforms raises a number of integrated elements. Biomarker discovery and initial selection needs to be integrated at the earliest stages with components that will allow systematic prioritization and triage of biomarker candidates. A number of important criteria need to be considered in selecting clinical biomarker candidates. Development of proof of concept assays and their optimization and validation represent an often overlooked feature of biomarker translational research. Initial assay optimization should confirm that assays can detect biomarkers in relevant clinical samples. Since access to human clinical samples is critical to iden-tification of biomarkers relevant to injury and disease as well as for assay development, design of human clinical validation studies is an important component of translational biomarker research platforms. Although these clinical studies share much in common with clinical trials for assessment of drug thera-peutic efficacy, there are a number of considerations unique to these efforts. Finally, platform selection and potential assay commercialization need to be considered. Decisions regarding whether or not to seek FDA approval also significantly influence translational research structures. Key words: Biomarkers , Brain injury , Translational research , Assay development , Clinical trials

  • Neuroproteomics and systems biology based discovery of protein biomarkers for traumatic brain injury and clinical validation
    Proteomics Clinical Applications, 2008
    Co-Authors: Firas Kobeissy, Monika W. Oli, Ronald L. Hayes, Shankar Sadasivan, Gillian Robinson, Stephen F. Larner, Zhiqun Zhang, Kevin K. W. Wang
    Abstract:

    The rapidly growing field of Neuroproteomics has expanded to track global proteomic changes underlying various neurological conditions such as traumatic brain injury (TBI), stroke, and Alzheimer's disease. TBI remains a major health problem with approximately 2 million incidents occurring annually in the United States, yet no affective treatment is available despite several clinical trials. The absence of brain injury diagnostic biomarkers was identified as a significant road-block to therapeutic development for brain injury. Recently, the field of Neuroproteomics has undertaken major advances in the area of neurotrauma research, where several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers in the field of TBI. One scope of this review is to evaluate the current status of TBI biomarker discovery using Neuroproteomics techniques, and at what stage we are at in their clinical validation. In addition, we will discuss the need for strengthening the role of systems biology and its application to the field of Neuroproteomics due to its integral role in establishing a comprehensive understanding of specific brain disorder and brain function in general. Finally, to achieve true clinical input of these neuroproteomic findings, these putative biomarkers should be validated using preclinical and clinical samples and linked to clinical diagnostic assays including ELISA or other high-throughput assays.

Hans Gerd Nothwang - One of the best experts on this subject based on the ideXlab platform.

  • Neuroproteomics the tasks lying ahead
    Electrophoresis, 2006
    Co-Authors: Michael Becker, Jens Schindler, Hans Gerd Nothwang
    Abstract:

    The brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is Neuroproteomics. Today's neuroscientists have access to a battery of versatile technologies both in transcriptomics and proteomics. The challenge is to choose the right strategy in order to generate new hypotheses on how the brain works. The goal of this review is therefore two-fold: first we recall the bewildering cellular, molecular, and functional complexity in the brain, as this knowledge is fundamental to any study design. In fact, an impressive complexity on the molecular level has recently re-emerged as a central theme in large-scale analyses. Then we review transcriptomics and proteomics technologies, as both are complementary. Finally, we comment on the most widely used proteomics techniques and their respective strengths and drawbacks. We conclude that for the time being, Neuroproteomics should focus on its strengths, namely the identification of posttranslational modifications and protein-protein interactions, as well as the characterization of highly purified subproteomes. For global expression profiling, emphasis should be put on further development to significantly increase coverage.

  • Neuroproteomics – the tasks lying ahead
    Electrophoresis, 2006
    Co-Authors: Michael Becker, Jens Schindler, Hans Gerd Nothwang
    Abstract:

    The brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is Neuroproteomics. Today's neuroscientists have access to a battery of versatile technologies both in transcriptomics and proteomics. The challenge is to choose the right strategy in order to generate new hypotheses on how the brain works. The goal of this review is therefore two-fold: first we recall the bewildering cellular, molecular, and functional complexity in the brain, as this knowledge is fundamental to any study design. In fact, an impressive complexity on the molecular level has recently re-emerged as a central theme in large-scale analyses. Then we review transcriptomics and proteomics technologies, as both are complementary. Finally, we comment on the most widely used proteomics techniques and their respective strengths and drawbacks. We conclude that for the time being, Neuroproteomics should focus on its strengths, namely the identification of posttranslational modifications and protein-protein interactions, as well as the characterization of highly purified subproteomes. For global expression profiling, emphasis should be put on further development to significantly increase coverage.

  • Review
    2005
    Co-Authors: Michael Becker, Jens Schindler, Hans Gerd Nothwang, Abteilung Tierphysiologie
    Abstract:

    Neuroproteomics – the tasks lying ahead The brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is Neuroproteomics. Today’s neuroscientists have access to a battery of versatile technologies both in transcriptomics and proteomics. The challenge is to choose the right strategy in order to generate new hypotheses on how the brain works. The goal of this review is therefore two-fold: first we recall the bewildering cellular, molecular, and functional complexity in the brain, as this knowledge is fundamental to any study design. In fact, an impressive complexity on the molecular level has recently re-emerged as a central theme in large-scale analyses. Then we review tran-scriptomics and proteomics technologies, as both are complementary. Finally, we comment on the most widely used proteomics techniques and their respective strengths and drawbacks. We conclude that for the time being, Neuroproteomics should focus on its strengths, namely the identification of posttranslational modifica-tions and protein–protein interactions, as well as the characterization of highly purified subproteomes. For global expression profiling, emphasis should be put on further development to significantly increase coverage

Zhiqun Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Recent updates on drug abuse analyzed by Neuroproteomics studies: Cocaine, Methamphetamine and MDMA
    Translational Proteomics, 2014
    Co-Authors: Firas Kobeissy, Kevin K. W. Wang, Zhiqun Zhang, Tarek H. Mouhieddine, Amaly Nokkari, Muhieddine M. Itani, Mohammed Mouhieddine, Rui Zhu, Mark S. Gold, Yehia Mechref
    Abstract:

    Abstract Currently, drug abuse and addiction represent a global public health concern with about 13.6 million people using illicit drugs in the USA alone. Substance abuse intervenes in normal brain functioning, causing alterations in memory, behavior and neuronal physiology. Although many studies have been conducted to elucidate the mode of action of different drugs, the heterogeneous modes of drug intake led to a complicated profile of drug-induced brain changes involving neurotoxicity and addiction. Given the complex interplay of genes and proteins in mediating these effects, Neuroproteomics analysis has been considered among the methods of choice to complement what has already been discovered and to create targeted therapies. In this review, we will focus on three drugs, namely cocaine, methamphetamine (METH) and 3,4-methylenedioxy-N-methylamphetamine (MDMA). In the context of Neuroproteomics, these drugs have been extensively studied by utilizing different experimental models, including primate and non-primate animals along with postmortem human samples. Even though there are many variations in the results, these drugs were shown to employ common pathways in eliciting their effects. Neuroproteomics analysis of these drugs has led to the identification of differentially expressed proteins involved in metabolism, oxidative stress, cell signaling, cytoskeleton, cell death and synaptic plasticity. Finally, this work will discuss recent findings from our laboratory by looking at a model of chronic methamphetamine abuse and its effect on different brain regions.

  • Neuroproteomics approach and neurosystems biology analysis: ROCK inhibitors as promising therapeutic targets in neurodegeneration and neurotrauma.
    Electrophoresis, 2012
    Co-Authors: Mohamad Raad, Kevin K. W. Wang, Zhiqun Zhang, Stefania Mondello, Tala El Tal, Rukhsana Gul, Rose-mary Boustany, Joy Guingab, Firas Kobeissy
    Abstract:

    Several common degenerative mechanisms and mediators underlying the neuronal injury pathways characterize several neurodegenerative diseases including Alzheimer's, Parkinson's, and Huntington's disease, as well as brain neurotrauma. Such common ground invites the emergence of new approaches and tools to study the altered pathways involved in neural injury alongside with neuritogenesis, an intricate process that commences with neuronal differentiation. Achieving a greater understanding of the impaired pathways of neuritogenesis would significantly help in uncovering detailed mechanisms of axonal regeneration. Among the several agents involved in neuritogenesis are the Rho and Rho kinases (ROCKs), which constitute key integral points in the Rho/ROCK pathway that is known to be disrupted in multiple neuropathologies such as spinal cord injury, traumatic brain injury, and Alzheimer's disease. This in turn renders ROCK inhibition as a promising candidate for therapeutic targets for treatment of neurodegenerative diseases. Among the novel tools to investigate the mechanisms involved in a specific disorder is the use of Neuroproteomics/systems biology approach, a growing subfield of bioinformatics aiming to study and establishing a global assessment of the entire neuronal proteome, addressing the dynamic protein changes and interactions. This review aims to examine recent updates regarding how Neuroproteomics aids in the understanding of molecular mechanisms of activation and inhibition in the area of neurogenesis and how Rho/ROCK pathway/ROCK inhibitors, primarily Y-27632 and Fasudil compounds, are applied in biological settings, promoting neuronal survival and neuroprotection that has direct future implications in neurotrauma.

  • Data Mining Strategies Applied in Brain Injury Models
    Data Mining for Biomarker Discovery, 2012
    Co-Authors: Stefania Mondello, Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Isaac Fingers, Kevin K. W. Wang
    Abstract:

    Traumatic brain injury or traumatic head injury is characterized as a direct physical impact or trauma to the head, causing brain injury. It represents a major national health problem without a US Food and Drug Administration-approved therapy. The application of Neuroproteomics/neurogenomics has revolutionized the characterization of protein/gene dynamics, leading to a greater understanding of post-injury biochemistry. Neuroproteomics and Neurogenomics fields have undertaken major advances in the area of neurotrauma research focusing on biomarker identification. Several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers utilizing these “omics approaches”. The identification of these differentially expressed candidate markers using these techniques is proving to be only the first step in the biomarker development process. However, to translate these findings into the clinic, data-driven development cycle incorporating data-mining steps for discovery, qualification, verification, and clinical validation is needed. Data mining steps extend beyond the collected data level into an integrated scheme of animal modeling, instrumentation, and functional data analysis. In this chapter, we provide an introductory review of data-mining/systems biology coupled approaches that have been applied to biomarker discovery and clinical validation; in addition, the need for strengthening the integral roles of these disciplines in establishing a comprehensive understanding of specific brain disorder and biomarker identification in general.

  • Leveraging biomarker platforms and systems biology for rehabilomics and biologics effectiveness research.
    Pm&r, 2011
    Co-Authors: Firas Kobeissy, Ronald L. Hayes, Zhiqun Zhang, Joy Guingab-cagmat, Razafsha, Laura E. O'steen, Wen Ta Chiu, Kevin K. W. Wang
    Abstract:

    Abstract Although traumatic brain injury (TBI) remains a major health problem, with approximately 2 million incidents occurring annually in the United States, no therapeutic agents to treat TBI have been approved by the Food and Drug Administration despite several clinical trials. It is estimated that 3.5 million Americans now have a lifelong condition that might be termed "chronic traumatic brain injury disease.'' Some health care providers categorize TBI as an "event" for which patients require brief periods of rehabilitation with no further treatment. On the contrary, TBI should be seen as a chronic disease process that fits the World Health Organization definition as being a non-reversible pathologic condition requiring special rehabilitation training. Among the major obstacles that contribute to this type of misconception is the absence of brain injury–specific diagnostic biomarker(s) that can indicate and monitor the long-term health status of patients with TBI after use of conventional therapeutics and a rehabilitation process. It is of interest that recent advances in genomics, proteomics, and systems biology have enabled us to use these high throughput–based approaches in developing biomarkers and therapeutic targets in the area of TBI. One aim of this article is to provide an overview that evaluates the current status of TBI biomarker discovery using Neuroproteomics/systems biology techniques, along with their clinical utilization. In addition, we discuss the need for strengthening the role of biomarker-based Neuroproteomics/systems biology and its potential utility in the field of rehabilitation, which would lead to the establishment of rehabilomics studies, where biomarkers would indicate and predict the long-term efficacy and health status of patients with chronic TBI conditions.

  • Methods in drug abuse Neuroproteomics: methamphetamine psychoproteome.
    Methods of Molecular Biology, 2009
    Co-Authors: Firas Kobeissy, Shankar Sadasivan, Zhiqun Zhang, Mark S. Gold, Kevin K. W. Wang
    Abstract:

    Methamphetamine (METH) is recognized as one of the most abused psychostimulants in the USA. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying MDMA and METH-induced neurotoxic effects both in vivo and in vitro. Our substance abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. Altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. Proteins that were shown to be downregulated included collapsin response mediator protein-2 (CRMP-2), superoxide dismutase 1 (SOD 1), and phosphatidylethanolamine-binding protein-1 (PEBP-1). Proteins that were shown to be upregulated included authophagy-linked microtubule-associated protein light chain 3 (LC3), synapsin-1, and Parkinsonism-linked ubiquitin carboxy-terminal hydroxylase-L1 (UCH-L1). This differential protein expression highlights on the neurotoxic mechanism involved in METH exposure as well as to discover potential markers for METH-induced neurotoxicity. In this chapter, we describe the current protocols for the in vivo rat model of acute METH treatment (40 mg/kg) coupled with the description of the multistep separation platform applied. These methods and protocols are discussed in the paradigm of acute model of methamphetamine drug abuse and can be applied to other models of substance abuse such as to MDMA or cocaine.