Advances in protein chemistry and structural biology最新文献

{"title":"Transmembrane protein TMEM230, regulator of metalloproteins and motor proteins in gliomas and gliosis.","authors":"Cinzia Cocola, Edoardo Abeni, Valentina Martino, Eleonora Piscitelli, Stefano Morara, Paride Pelucchi, Ettore Mosca, Alice Chiodi, Tasnim Mohamed, Mira Palizban, Giuseppina De Petro, Giovanni Porta, Burkhard Greve, Alessio Noghero, Valerio Magnaghi, Gianfranco Bellipanni, James Kehler, Martin Götte, Federico Bussolino, Luciano Milanesi, Ileana Zucchi, Rolland Reinbold","doi":"10.1016/bs.apcsb.2024.03.006","DOIUrl":"10.1016/bs.apcsb.2024.03.006","url":null,"abstract":"<p><p>Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"255-297"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic and predictive abilities of myokines in patients with heart failure.","authors":"Oleksandr O Berezin, Tetiana A Berezina, Uta C Hoppe, Michael Lichtenauer, Alexander E Berezin","doi":"10.1016/bs.apcsb.2023.12.021","DOIUrl":"10.1016/bs.apcsb.2023.12.021","url":null,"abstract":"<p><p>Myokines are defined as a heterogenic group of numerous cytokines, peptides and metabolic derivates, which are expressed, synthesized, produced, and released by skeletal myocytes and myocardial cells and exert either auto- and paracrine, or endocrine effects. Previous studies revealed that myokines play a pivotal role in mutual communications between skeletal muscles, myocardium and remote organs, such as brain, vasculature, bone, liver, pancreas, white adipose tissue, gut, and skin. Despite several myokines exert complete divorced biological effects mainly in regulation of skeletal muscle hypertrophy, residential cells differentiation, neovascularization/angiogenesis, vascular integrity, endothelial function, inflammation and apoptosis/necrosis, attenuating ischemia/hypoxia and tissue protection, tumor growth and malignance, for other occasions, their predominant effects affect energy homeostasis, glucose and lipid metabolism, adiposity, muscle training adaptation and food behavior. Last decade had been identified 250 more myokines, which have been investigating for many years further as either biomarkers or targets for heart failure management. However, only few myokines have been allocated to a promising tool for monitoring adverse cardiac remodeling, ischemia/hypoxia-related target-organ dysfunction, microvascular inflammation, sarcopenia/myopathy and prediction for poor clinical outcomes among patients with HF. This we concentrate on some most plausible myokines, such as myostatin, myonectin, brain-derived neurotrophic factor, muslin, fibroblast growth factor 21, irisin, leukemia inhibitory factor, developmental endothelial locus-1, interleukin-6, nerve growth factor and insulin-like growth factor-1, which are suggested to be useful biomarkers for HF development and progression.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"45-98"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut dysbiosis and neurological modalities: An engineering approach via proteomic analysis of gut-brain axis.","authors":"Meenakshi Kandpal, Nidhi Varshney, Kunal Sameer Rawal, Hem Chandra Jha","doi":"10.1016/bs.apcsb.2024.02.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.02.001","url":null,"abstract":"<p><p>The human gut microbiota is a complex and dynamic community of microorganisms, that influence metabolic, neurodevelopmental, and immune pathways. Microbial dysbiosis, characterized by changes in microbial diversity and relative abundances, is implicated in the development of various chronic neurological and neurodegenerative disorders. These disorders are marked by the accumulation of pathological protein aggregates, leading to the progressive loss of neurons and behavioural functions. Dysregulations in protein-protein interaction networks and signalling complexes, critical for normal brain function, are common in neurological disorders but challenging to unravel, particularly at the neuron and synapse-specific levels. To advance therapeutic strategies, a deeper understanding of neuropathogenesis, especially during the progressive disease phase, is needed. Biomarkers play a crucial role in identifying disease pathophysiology and monitoring disease progression. Proteomics, a powerful technology, shows promise in accelerating biomarker discovery and aiding in the development of novel treatments. In this chapter, we provide an in-depth overview of how proteomic techniques, utilizing various biofluid samples from patients with neurological conditions and diverse animal models, have contributed valuable insights into the pathogenesis of numerous neurological disorders. We also discuss the current state of research, potential challenges, and future directions in proteomic approaches to unravel neuro-pathological conditions.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"199-248"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in plant translational genomics for crop improvement.","authors":"Shivangi Mathur, Deeksha Singh, Rajiv Ranjan","doi":"10.1016/bs.apcsb.2023.11.009","DOIUrl":"10.1016/bs.apcsb.2023.11.009","url":null,"abstract":"<p><p>The growing population, climate change, and limited agricultural resources put enormous pressure on agricultural systems. A plateau in crop yields is occurring and extreme weather events and urbanization threaten the livelihood of farmers. It is imperative that immediate attention is paid to addressing the increasing food demand, ensuring resilience against emerging threats, and meeting the demand for more nutritious, safer food. Under uncertain conditions, it is essential to expand genetic diversity and discover novel crop varieties or variations to develop higher and more stable yields. Genomics plays a significant role in developing abundant and nutrient-dense food crops. An alternative to traditional breeding approach, translational genomics is able to improve breeding programs in a more efficient and precise manner by translating genomic concepts into practical tools. Crop breeding based on genomics offers potential solutions to overcome the limitations of conventional breeding methods, including improved crop varieties that provide more nutritional value and are protected from biotic and abiotic stresses. Genetic markers, such as SNPs and ESTs, contribute to the discovery of QTLs controlling agronomic traits and stress tolerance. In order to meet the growing demand for food, there is a need to incorporate QTLs into breeding programs using marker-assisted selection/breeding and transgenic technologies. This chapter primarily focuses on the recent advances that are made in translational genomics for crop improvement and various omics techniques including transcriptomics, metagenomics, pangenomics, single cell omics etc. Numerous genome editing techniques including CRISPR Cas technology and their applications in crop improvement had been discussed.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"335-382"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From genome to clinic: The power of translational bioinformatics in improving human health.","authors":"Satyendra Singh, Anurag Kumar Pandey, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2023.11.010","DOIUrl":"10.1016/bs.apcsb.2023.11.010","url":null,"abstract":"<p><p>Translational bioinformatics (TBI) has transformed healthcare by providing personalized medicine and tailored treatment options by integrating genomic data and clinical information. In recent years, TBI has bridged the gap between genome and clinical data because of significant advances in informatics like quantum computing and utilizing state-of-the-art technologies. This chapter discusses the power of translational bioinformatics in improving human health, from uncovering disease-causing genes and variations to establishing new therapeutic techniques. We discuss key application areas of bioinformatics in clinical genomics, such as data sources and methods used in translational bioinformatics, the impact of translational bioinformatics on human health, and how machine learning and artificial intelligence are being used to mine vast amounts of data for drug development and precision medicine. We also look at the problems, constraints, and ethical concerns connected with exploiting genomic data and the future of translational bioinformatics and its potential impact on medicine and human health. Ultimately, this chapter emphasizes the great potential of translational bioinformatics to alter healthcare and enhance patient outcomes.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-protein interaction network analysis for the identification of novel multi-target inhibitors and target miRNAs against Alzheimer's disease.","authors":"Vinay Kumar, Kunal Roy","doi":"10.1016/bs.apcsb.2023.11.005","DOIUrl":"10.1016/bs.apcsb.2023.11.005","url":null,"abstract":"<p><p>This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"405-467"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational bioinformatics approach to combat cardiovascular disease and cancers.","authors":"Shahjahan, Joy Kumar Dey, Sanjay Kumar Dey","doi":"10.1016/bs.apcsb.2023.11.006","DOIUrl":"10.1016/bs.apcsb.2023.11.006","url":null,"abstract":"<p><p>Bioinformatics is an interconnected subject of science dealing with diverse fields including biology, chemistry, physics, statistics, mathematics, and computer science as the key fields to answer complicated physiological problems. Key intention of bioinformatics is to store, analyze, organize, and retrieve essential information about genome, proteome, transcriptome, metabolome, as well as organisms to investigate the biological system along with its dynamics, if any. The outcome of bioinformatics depends on the type, quantity, and quality of the raw data provided and the algorithm employed to analyze the same. Despite several approved medicines available, cardiovascular disorders (CVDs) and cancers comprises of the two leading causes of human deaths. Understanding the unknown facts of both these non-communicable disorders is inevitable to discover new pathways, find new drug targets, and eventually newer drugs to combat them successfully. Since, all these goals involve complex investigation and handling of various types of macro- and small- molecules of the human body, bioinformatics plays a key role in such processes. Results from such investigation has direct human application and thus we call this filed as translational bioinformatics. Current book chapter thus deals with diverse scope and applications of this translational bioinformatics to find cure, diagnosis, and understanding the mechanisms of CVDs and cancers. Developing complex yet small or long algorithms to address such problems is very common in translational bioinformatics. Structure-based drug discovery or AI-guided invention of novel antibodies that too with super-high accuracy, speed, and involvement of considerably low amount of investment are some of the astonishing features of the translational bioinformatics and its applications in the fields of CVDs and cancers.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"221-261"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vesicle transport of matrix metalloproteinases.","authors":"Yoshifumi Itoh","doi":"10.1016/bs.apcsb.2024.03.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.03.001","url":null,"abstract":"<p><p>Multicellular organisms consist of cells and extracellular matrix (ECM). ECM creates a cellular microenvironment, and cells locally degrade the ECM according to their cellular activity. A major group of enzymes that modify ECM belongs to matrix metalloproteinases (MMPs) and play major roles in various pathophysiological events. ECM degradation by MMPs does not occur in all cellular surroundings but only where it is necessary, and cells achieve this by directionally secreting these proteolytic enzymes. Recent studies have indicated that such enzyme secretion is achieved by targeted vesicle transport along the microtubules, and several kinesin superfamily proteins (KIFs) have been identified as responsible motor proteins involved in the processes. This chapter discusses recent findings of the vesicle transport of MMPs and their roles.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"361-380"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering immune response to regulate cardiovascular disease and cancer.","authors":"Diksha Rani, Smaranjot Kaur, Shahjahan, Joy Kumar Dey, Sanjay Kumar Dey","doi":"10.1016/bs.apcsb.2023.12.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.004","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) and cancer are major contributors to global morbidity and mortality. This book chapter delves into the intricate relationship between the immune system and the pathogenesis of both cardiovascular and cancer diseases, exploring the roles of innate and adaptive immunities, immune regulation, and immunotherapy in these complex conditions. The innate immune system acts as the first line of defense against tissue damage and infection, with a significant impact on the initiation and progression of CVD and cancer. Endothelial dysfunction, a hallmark in CVD, shares commonalities with the tumor microenvironment in cancer, emphasizing the parallel involvement of the immune system in both conditions. The adaptive immune system, particularly T cells, contributes to prolonged inflammation in both CVD and cancer. Regulatory T cells and the intricate balance between different T cell subtypes influence disease progression, wound healing, and the outcomes of ischemic injury and cancer immunosurveillance. Dysregulation of immune homeostasis can lead to chronic inflammation, contributing to the development and progression of both CVD and cancer. Thus, immunotherapy emerged as a promising avenue for preventing and managing these diseases, with strategies targeting immune cell modulation, cytokine manipulation, immune checkpoint blockade, and tolerance induction. The impact of gut microbiota on CVD and cancer too is explored in this chapter, highlighting the role of gut leakiness, microbial metabolites, and the potential for microbiome-based interventions in cardiovascular and cancer immunotherapies. In conclusion, immunomodulatory strategies and immunotherapy hold promise in reshaping the landscape of cardiovascular and cancer health. Additionally, harnessing the gut microbiota for immune modulation presents a novel approach to prevent and manage these complex diseases, emphasizing the importance of personalized and precision medicine in healthcare. Ongoing research and clinical trials are expected to further elucidate the complex immunological underpinnings of CVD and cancer thereby refining these innovative approaches.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"381-417"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy guided precision medicine in solid tumors.","authors":"Sanjana Mehrotra, Manu Kupani, Jaismeen Kaur, Jashandeep Kaur, Rajeev Kumar Pandey","doi":"10.1016/bs.apcsb.2024.02.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.02.004","url":null,"abstract":"<p><p>Cancer is no longer recognized as a single disease but a collection of diseases each with its defining characteristics and behavior. Even within the same cancer type, there can be substantial heterogeneity at the molecular level. Cancer cells often accumulate various genetic mutations and epigenetic alterations over time, leading to a coexistence of distinct subpopulations of cells within the tumor. This tumor heterogeneity arises not only due to clonal outgrowth of cells with genetic mutations, but also due to interactions of tumor cells with the tumor microenvironment (TME). The latter is a dynamic ecosystem that includes cancer cells, immune cells, fibroblasts, endothelial cells, stromal cells, blood vessels, and extracellular matrix components, tumor-associated macrophages and secreted molecules. The complex interplay between tumor heterogeneity and the TME makes it difficult to develop one-size-fits-all treatments and is often the cause of therapeutic failure and resistance in solid cancers. Technological advances in the post-genomic era have given us cues regarding spatial and temporal tumor heterogeneity. Armed with this knowledge, oncologists are trying to target the unique genomic, epigenetic, and molecular landscape in the tumor cell that causes its oncogenic transformation in a particular patient. This has ushered in the era of personalized precision medicine (PPM). Immunotherapy, on the other hand, involves leveraging the body's immune system to recognize and attack cancer cells and spare healthy cells from the damage induced by radiation and chemotherapy. Combining PPM and immunotherapy represents a paradigm shift in cancer treatment and has emerged as a promising treatment modality for several solid cancers. In this chapter, we summarise major types of cancer immunotherapy and discuss how they are being used for precision medicine in different solid tumors.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"249-292"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}