In spite of the rapid advances in the development of the new proteomic technologies, there are, to date, relatively fewer studies aiming to explore the neuronal proteome. One of the reasons is the complexity of the brain, which presents high cellular heterogeneity and a unique subcellular compartmentalization. Therefore, tissue fractionation of the brain to enrich proteins of interest will reduce the complexity of the proteomics approach leading to the production of manageable and meaningful results. In this review, general considerations and strategies of proteomics, the advantages and challenges to exploring the neuronal proteome are described and summarized. In addition, this article presents an overview of recent advances of proteomic technologies and shows that proteomics can serve as a valuable tool to globally explore the changes in brain proteome during various disease states. Understanding the molecular basis of brain function will be extremely useful in identifying novel targets for the treatment of brain diseases. 相似文献
Schistosomiasis is a neglected tropical disease of clinical significance that, despite years of research, still requires an effective vaccine and improved diagnostics for surveillance, control and potential elimination. Furthermore, the causes of host pathology during schistosomiasis are still not completely understood. The recent sequencing of the genomes of the three key schistosome species has enabled the discovery of many new possible vaccine and drug targets, as well as diagnostic biomarkers, using high-throughput and sensitive proteomics methods. This review focuses on the literature of the last 5 years that has reported on the use of proteomics to both better understand the biology of the schistosome parasites and the disease they cause in definitive mammalian hosts. 相似文献
Introduction: Cancer is the second most common cause of death worldwide and its heterogeneity complicates therapy. Standard cytotoxic regiments disrupt rapidly dividing cells, regardless of their neoplastic status. The introduction of less toxic targeted therapies has partially contributed to the observed decrease in cancer-related mortality. Cell-surface proteins represent attractive targets for therapy, due to their easily-accessible localization and their involvement in essential signaling pathways, often dysregulated in cancer. Despite their clinical appeal, cell-surface proteins are often underrepresented in standard proteomic data sets, due to their poor solubility and lower expression levels compared to intracellular proteins.
Areas covered: This review will summarize some of the available techniques for enriching the cell-surface proteome, and discuss their advantages, limitations and applicability to clinical sample-testing. Moreover, we discuss currently available strategies for the development of novel targeted therapies in cancer.
Expert commentary: The interest in elucidating the cancer-associated surfaceome is growing and will likely benefit from recent advancements in instrument sensitivity, method development, and a growing body of high-quality proteomics databases. Multiomics studies, in combination with functional validations (e.g. dropout screens), and evaluation of the healthy surfaceome, will likely aid in the selection of relevant targets for future therapy development. 相似文献
Neisseria meningitidis (meningococcus) is a major causative organism of meningitis and sepsis and Neisseria gonorrhoeae (gonococcus) is the causative organism of the sexually transmitted disease gonorrhea. Infections caused by meningococci are vaccine-preventable, whereas gonococcal vaccine research and development has languished for decades and the correlates of protection are still largely unknown. In the past two decades, complementary ‘omic’ platforms have been developed to interrogate Neisseria genomes and gene products. Proteomic techniques applied to whole Neisseria bacteria, outer membranes and outer membrane vesicle vaccines have generated protein maps and also allowed the examination of environmental stresses on protein expression. In particular, immuno-proteomics has identified proteins whose expression is correlated with the development of human natural immunity to meningococcal infection and colonization and following vaccination. Neisseria proteomic techniques have produced a catalog of potential vaccine antigens and investigating the functional and biological properties of these proteins could finally provide ‘universal’ Neisseria vaccines. 相似文献
Mesenchymal stem or stromal cells (MSCs) have become of great interest for cell-based therapy owing to their roles in tissue repair and immune suppression. MSCs have the ability to differentiate into specialized tissues, including bone, cartilage and muscle, among several others. Furthermore, it has been found that MSCs can also serve as cellular factories that secrete mediators to stimulate in situ regeneration of injured tissues. Proteomics has contributed significantly to the identification of new proteins to improve cellular characterization of MSCs, to identify new targets for therapeutic intervention and to elucidate important pathways utilized by MSCs to differentiate into distinct tissues. As proteomics technology advances, several studies can be revisited and analyzed in depth, employing state-of-the-art approaches, helping to uncover the cellular mechanisms utilized by MSCs to exert their regenerative functionalities. In this article, we will review the progress made so far and discuss further opportunities for proteomics to contribute to the clinical applications of MSCs. 相似文献
Finding an efficient neuroprotectant is of urgent need in the field of stroke research. The goal of this study was to test the effect of acute simvastatin administration after stroke in a rat embolic model and to explore its mechanism of action through brain proteomics. To that end, male Wistar rats were subjected to a Middle Cerebral Arteria Occlusion and simvastatin (20 mg/kg s.c) (n = 11) or vehicle (n = 9) were administered 15 min after. To evaluate the neuroprotective mechanisms of simvastatin, brain homogenates after 48 h were analyzed by two‐dimensional fluorescence Difference in Gel Electrophoresis (DIGE) technology. We confirmed that simvastatin reduced the infarct volume and improved neurological impairment at 48 h after the stroke in this model. Considering our proteomics analysis, 66 spots, which revealed significant differences between groups, were analyzed by matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry allowing the identification of 27 proteins. From these results, we suggest that simvastatin protective effect can be partly explained by the attenuation of the oxidative and stress response at blood–brain barrier level after cerebral ischemia. Interestingly, analyzing one of the proteins (HSP75) in plasma from stroke patients who had received simvastatin during the acute phase, we confirmed the results found in the pre‐clinical model.
There is a compelling clinical need for adjuvants suitable for human use to enhance the efficacy of vaccines in the prevention of life-threatening infection. Candidate populations for such vaccine-adjuvant strategies include normal individuals at the two extremes of life, as well as the ever increasing population of immunocompromised individuals. In addition, adjuvants that would increase the efficiency of vaccination with such vaccines as those directed against hepatitis B andStreptococcus pneumoniae would have an even greater general use. Cytokines, as natural peptides intimately involved in the normal immune response, have great appeal as potential adjuvants. An increasing body of work utilizing recombinant versions of interleukin-1, -2, -3, -6, -12, gamma-interferon, tumor necrosis factor, and granulocyte-monocyte-colony stimulating factor has shown that cytokines do have vaccine adjuvant activity. However, in order to optimize adjuvant effect and minimize systemic toxicity, strategies in which the cytokine is fused to the antigen, or the cytokine is presented within liposomes or microspheres appear to be necessary to make this a practical approach suitable for human use. There is much promise in this approach, but there is much work to be accomplished in order to optimize the pharmacokinetics of cytokine administration as well as its side effect profile.Abbreviations IL
interleukin
- TNF
tumor necrosis factor
- NK
natural killer
- pIL-1
interleukin-1 peptide
- LPS
lipopolysaccharide
- r
recombinant
- HSV-2
herpes simplex virus 2
-
gamma 相似文献
Introduction: Calmodulin (CaM) is a highly conserved Ca2+-binding protein that is exceptionally abundant in the brain. In the presynaptic compartment of neurons, CaM transduces changes in Ca2+ concentration into the regulation of synaptic transmission dynamics.
Areas covered: We review selected literature including published CaM interactor screens and outline established and candidate presynaptic CaM targets. We present a workflow of biochemical and structural proteomic methods that were used to identify and characterize the interactions between CaM and Munc13 proteins. Finally, we outline the potential of ion mobility-mass spectrometry (IM-MS) for conformational screening and of protein-protein cross-linking for the structural characterization of CaM complexes.
Expert commentary: Cross-linking/MS and native MS can be applied with considerable throughput to protein mixtures under near-physiological conditions, and thus effectively complement high-resolution structural biology techniques. Experimental distance constraints are applicable best when obtained by combining different cross-linking strategies, i.e. by using cross-linkers with different spacer length and reactivity, and by using the incorporation of unnatural photo-reactive amino acids. Insights from structural proteomics can be used to generate CaM-insensitive mutants of CaM targets for functional studies in vitro or ideally in vivo. 相似文献
Introduction: Unwanted platelet activation is associated with numerous diseases, mainly thrombosis-related. In this context, proteomics has emerged as a novel tool with potential for drug target discovery and to scrutinize the effects of antiplatelet drugs.
Areas covered: The present review presents the main findings of platelet proteomic studies to date in the context of drug target discovery and perspectives for the future ahead. It includes data and evidences obtained from literature searches on PubMed as well as commentaries derived from the authors’ experience and opinions.
Expert commentary: Platelet proteomics applied to drug target discovery is a young field. Recent studies have shown promising data, especially in the context of coronary artery disease. However, challenges remain such as establishing definitive guidelines for blood collection and platelet isolation, essential to guarantee data reproducibility. Recent advances in quantitative platelet proteomics should lead to novel studies with higher clinical impact in the near future. 相似文献