H. Singh, Ashmeet Kaur, Ishpreet Kaur, H. Buttar, S. Bhullar
Nanotechnology is rapidly advancing and will leave no field untouched by its ground breaking innovations. Nanoparticles are molecules with a diameter ranging from 10-100 nm. Nanotechnology has promising biomedical applications and most noteworthy amongst them are noble metal particles. For instance, gold nanoparticles (AuNPs) provide a unique blend of physical and optical properties, chemical inertness, and high surface to volume ratio. They can be synthesized as well as functionalised to support various ligands on their surface. Their surface functionalization and diverse properties render the gold nanoparticles highly useful for drug delivery and gene carrier for therapeutic purposes and as molecular probes for disease diagnosis. The foundation for the usage of AuNPs in therapeutics and diagnosis was laid by the ancient studies done with ruby gold for curing diseases in middle ages. Presently, AuNPs have become available in different types such as spheres, rods, shells, cages and SERS particles which vary in shape, size and physical properties. The biomedical applications of these particles include drug and gene delivery, cancer diagnosis and therapy, determination of biological molecules and microorganisms, detection of disease etiology, immunoassay, enzyme immobilization, etc. Overall, the focus of this review is to highlight that AuNPs provide an excellent platform for the discovery of new therapies, cure for certain cancers, molecular probe for diagnostic purposes, as well as gene carriers and drug delivery vehicles. Biomed Rev 2015; 26: 23-36. Key words: gold nanoparticles, cancer treatment, drug delivery system, gold nanocarrier therapy
{"title":"GOLD NANOPARTICLES: A PROMISING THERAPEUTIC APPROACH","authors":"H. Singh, Ashmeet Kaur, Ishpreet Kaur, H. Buttar, S. Bhullar","doi":"10.14748/BMR.V26.1541","DOIUrl":"https://doi.org/10.14748/BMR.V26.1541","url":null,"abstract":"Nanotechnology is rapidly advancing and will leave no field untouched by its ground breaking innovations. Nanoparticles are molecules with a diameter ranging from 10-100 nm. Nanotechnology has promising biomedical applications and most noteworthy amongst them are noble metal particles. For instance, gold nanoparticles (AuNPs) provide a unique blend of physical and optical properties, chemical inertness, and high surface to volume ratio. They can be synthesized as well as functionalised to support various ligands on their surface. Their surface functionalization and diverse properties render the gold nanoparticles highly useful for drug delivery and gene carrier for therapeutic purposes and as molecular probes for disease diagnosis. The foundation for the usage of AuNPs in therapeutics and diagnosis was laid by the ancient studies done with ruby gold for curing diseases in middle ages. Presently, AuNPs have become available in different types such as spheres, rods, shells, cages and SERS particles which vary in shape, size and physical properties. The biomedical applications of these particles include drug and gene delivery, cancer diagnosis and therapy, determination of biological molecules and microorganisms, detection of disease etiology, immunoassay, enzyme immobilization, etc. Overall, the focus of this review is to highlight that AuNPs provide an excellent platform for the discovery of new therapies, cure for certain cancers, molecular probe for diagnostic purposes, as well as gene carriers and drug delivery vehicles. Biomed Rev 2015; 26: 23-36. Key words: gold nanoparticles, cancer treatment, drug delivery system, gold nanocarrier therapy","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"195 1","pages":"23-36"},"PeriodicalIF":0.0,"publicationDate":"2015-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76867451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We commence this review by outlining the challenges faced by physical theories of consciousness and briefly describe the two main approaches based on classical or quantum mechanics. Next, we provide a detailed exposition of the motivation, the theoretical construction and experimental falsification of the celebrated model due to Beck and Eccles concerning mind-brain interaction purported to operate at the sites of neurotransmitter release in the brain. Finally, we propose our own model of a vibrationally assisted quantum tunneling mechanism involving a Davydov soliton propagating along the hydrogen bonds in the protein four-α-helix bundle of the SNARE complex (soluble NSF attachment protein receptor; NSF, N-ethylmaleimide sensitive fusion proteins) that drives synaptic vesicle fusion. We also discuss the possible experimental tests that could falsify our model. Since erasure of consciousness by volatile anesthetics results from binding to the hydrophobic core of the SNARE four-α-helix bundle, our model is well suited to support quantum interactive dualism. Biomedical Reviews 2014; 25: 15-24.
我们首先概述了意识的物理理论所面临的挑战，并简要描述了基于经典力学或量子力学的两种主要方法。接下来，我们详细阐述了Beck和Eccles关于大脑中神经递质释放部位的心脑相互作用的著名模型的动机、理论构建和实验证伪。最后，我们提出了我们自己的振动辅助量子隧穿机制模型，涉及Davydov孤子沿着SNARE复合体(可溶性NSF附着蛋白受体;NSF, n -乙基马来酰亚胺敏感融合蛋白)驱动突触囊泡融合。我们还讨论了可能证伪我们模型的实验测试。由于挥发性麻醉剂的意识消除是由于与SNARE 4 -α-螺旋束的疏水核心结合造成的，因此我们的模型非常适合支持量子相互作用二元论。生物医学评论2014;25: 15 - 24。
{"title":"Quantum interactive dualism: From Beck and Eccles tunneling model of exocytosis to molecular biology of SNARE zipping","authors":"Danko D. Georgiev, J. Glazebrook","doi":"10.14748/BMR.V25.1038","DOIUrl":"https://doi.org/10.14748/BMR.V25.1038","url":null,"abstract":"We commence this review by outlining the challenges faced by physical theories of consciousness and briefly describe the two main approaches based on classical or quantum mechanics. Next, we provide a detailed exposition of the motivation, the theoretical construction and experimental falsification of the celebrated model due to Beck and Eccles concerning mind-brain interaction purported to operate at the sites of neurotransmitter release in the brain. Finally, we propose our own model of a vibrationally assisted quantum tunneling mechanism involving a Davydov soliton propagating along the hydrogen bonds in the protein four-α-helix bundle of the SNARE complex (soluble NSF attachment protein receptor; NSF, N-ethylmaleimide sensitive fusion proteins) that drives synaptic vesicle fusion. We also discuss the possible experimental tests that could falsify our model. Since erasure of consciousness by volatile anesthetics results from binding to the hydrophobic core of the SNARE four-α-helix bundle, our model is well suited to support quantum interactive dualism. Biomedical Reviews 2014; 25: 15-24.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"119 1","pages":"15-24"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73163644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autism spectrum disorders (ASD) is a group of lifelong neurodevelopmental disorders characterized by impairment in social interaction and communication, delayed and disordered language, restricted and stereotypic patterns of behaviour, interests and activities, and onset before 3 years of age.
{"title":"Autism spectrum disorders: neurotrophins enter the dance","authors":"Rouzha Pancheva, M. Georgieva","doi":"10.14748/BMR.V25.1051","DOIUrl":"https://doi.org/10.14748/BMR.V25.1051","url":null,"abstract":"Autism spectrum disorders (ASD) is a group of lifelong neurodevelopmental disorders characterized by impairment in social interaction and communication, delayed and disordered language, restricted and stereotypic patterns of behaviour, interests and activities, and onset before 3 years of age.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"6 1","pages":"93-99"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86331916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: There are prominent discrepancies in the general approaches of psychology and psychiatry, many of them due to diverse and incompatible tacit positions on the mind-brain debate (MBD). For this reason we need to enhance the dialogue with neurosciences and other human sciences relevant to the problems of psychopathology. To achieve such goal we can reduce the level of diversity of mind-brain problem project-solutions as implied in different theoretical models and practices. Arguments: I shall trace the MBD to the one of the most relevant for the modern psychopathology areas: the group of neurosciences. We seek the interference of the philosophical assumptions, the evidence of neuroscience and the development of psychopathology. We prove by a post rem analysis that the reduced group of predominant project-solutions of MBD excludes genuine forms of dualism and extreme forms of physicalism (like epiphenomenalism or eliminative materialism). Conclusion: A predominant group of project-solutions is adopted including complementary combination of contemporary forms of physicalism: identity theory of mind applied to mental events and brain processes; supervenience principle applied to other mental phenomena. Biomedical Reviews 2011; 22: 65-76.
{"title":"A linkage of mind and brain: towards translational validity between neurobiology and psychiatry","authors":"D. Stoyanov","doi":"10.14748/BMR.V22.36","DOIUrl":"https://doi.org/10.14748/BMR.V22.36","url":null,"abstract":"Aim: There are prominent discrepancies in the general approaches of psychology and psychiatry, many of them due to diverse and incompatible tacit positions on the mind-brain debate (MBD). For this reason we need to enhance the dialogue with neurosciences and other human sciences relevant to the problems of psychopathology. To achieve such goal we can reduce the level of diversity of mind-brain problem project-solutions as implied in different theoretical models and practices. Arguments: I shall trace the MBD to the one of the most relevant for the modern psychopathology areas: the group of neurosciences. We seek the interference of the philosophical assumptions, the evidence of neuroscience and the development of psychopathology. We prove by a post rem analysis that the reduced group of predominant project-solutions of MBD excludes genuine forms of dualism and extreme forms of physicalism (like epiphenomenalism or eliminative materialism). Conclusion: A predominant group of project-solutions is adopted including complementary combination of contemporary forms of physicalism: identity theory of mind applied to mental events and brain processes; supervenience principle applied to other mental phenomena. Biomedical Reviews 2011; 22: 65-76.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"216 1","pages":"65-76"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85355114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Sequeira, Ginpreet Kaur, M. Chintamaneni, H. Buttar
Lactose intolerance is a common disorder affecting an individual's ability to digest lactose present in milk or any food product. Lactose intolerance is caused by the deficiency of β-galactosidase (lactase) in the digestive tract. Diagnosis of lactose intolerance is not so simple and straightforward clinically. Many biochemical and genetic tests have been developed for the determination of lactose intolerance. Several case reports indicate wherein subjects have self-diagnosed being lactose intolerant. There is an emerging link of this disorder with human gene polymorphism, where genetic basis has been used as a diagnostic tool. The high prevalence of this condition among children and adults has compelled the production of lactose-free foods. Additionally, external enzyme supplementation has been looked at as an alternative protective mechanism in lactose intolerant subjects. This review highlights the genetic variants of lactase polymorphism and theranostic (therapeutic and diagnostic) strategies for lactose intolerance. Biomedical Reviews 2014; 25: 35-44.
{"title":"Lactose intolerance: genetics of lactase polymorphisms, diagnosis and novel therapy","authors":"E. Sequeira, Ginpreet Kaur, M. Chintamaneni, H. Buttar","doi":"10.14748/BMR.V25.1046","DOIUrl":"https://doi.org/10.14748/BMR.V25.1046","url":null,"abstract":"Lactose intolerance is a common disorder affecting an individual's ability to digest lactose present in milk or any food product. Lactose intolerance is caused by the deficiency of β-galactosidase (lactase) in the digestive tract. Diagnosis of lactose intolerance is not so simple and straightforward clinically. Many biochemical and genetic tests have been developed for the determination of lactose intolerance. Several case reports indicate wherein subjects have self-diagnosed being lactose intolerant. There is an emerging link of this disorder with human gene polymorphism, where genetic basis has been used as a diagnostic tool. The high prevalence of this condition among children and adults has compelled the production of lactose-free foods. Additionally, external enzyme supplementation has been looked at as an alternative protective mechanism in lactose intolerant subjects. This review highlights the genetic variants of lactase polymorphism and theranostic (therapeutic and diagnostic) strategies for lactose intolerance. Biomedical Reviews 2014; 25: 35-44.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"358 1","pages":"35-44"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80190895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Mahdi, R. F. Bedeer, A. Gabr, Huda Eltahry, M. Berger
Endothelin system members including endothelin-1, endothelin-2, endothelin-3, endothelin receptors, and endothelin converting enzyme are considered major regulating factors in cancer cell biology and cancer microenvironment. Endothelins are members of the matrix metalloproteinase superfamily of proteases, which are released from pre-proteins, bind to their receptors with differential affinity, and are degraded following cellular uptake. For their structural similarity, endothelin-2 and endothelin-3 can be regarded as natural competitors for the endothelin-1 receptors and as natural antagonists of endothelin-1. Endothelin-1 is regulated at several levels, primarily at the level of transcription. Remarkably, endothelin-1 is overexpressed in colorectal cancer, and elevated plasma levels were found in colorectal cancer patients. Endothelin receptor type A has an unequal distribution in the colon, as it is over-expressed in the proximal and distal segments of the colon. Compared with normal mucosal tissue, there is high expression of endothelin receptor type A and low expression of endothelin receptor type B in colorectal cancer at all Dukes stages. By binding to endothelin receptor type A, endothelin-1 leads to down-regulation of epithelial and increased expression of mesenchymal markers. Also, endothelin-1 acts as anti-apoptotic factor through multiple pathways like PI3K-dependent AKT activation or NF-κB signaling. Members of the endothelin system might be used as cancer biomarker and from a therapeutic point of view, targeting the endothelin axis is a promising aim. In effect, potential drugs may include endothelin converting enzyme inhibitors as well as selective and non-selective antagonists of endothelin receptor types A and B. Biomedical Reviews 2014; 25: 1-13.
{"title":"Aspects of the endothelin system in colorectal cancer","authors":"M. Mahdi, R. F. Bedeer, A. Gabr, Huda Eltahry, M. Berger","doi":"10.14748/BMR.V25.1042","DOIUrl":"https://doi.org/10.14748/BMR.V25.1042","url":null,"abstract":"Endothelin system members including endothelin-1, endothelin-2, endothelin-3, endothelin receptors, and endothelin converting enzyme are considered major regulating factors in cancer cell biology and cancer microenvironment. Endothelins are members of the matrix metalloproteinase superfamily of proteases, which are released from pre-proteins, bind to their receptors with differential affinity, and are degraded following cellular uptake. For their structural similarity, endothelin-2 and endothelin-3 can be regarded as natural competitors for the endothelin-1 receptors and as natural antagonists of endothelin-1. Endothelin-1 is regulated at several levels, primarily at the level of transcription. Remarkably, endothelin-1 is overexpressed in colorectal cancer, and elevated plasma levels were found in colorectal cancer patients. Endothelin receptor type A has an unequal distribution in the colon, as it is over-expressed in the proximal and distal segments of the colon. Compared with normal mucosal tissue, there is high expression of endothelin receptor type A and low expression of endothelin receptor type B in colorectal cancer at all Dukes stages. By binding to endothelin receptor type A, endothelin-1 leads to down-regulation of epithelial and increased expression of mesenchymal markers. Also, endothelin-1 acts as anti-apoptotic factor through multiple pathways like PI3K-dependent AKT activation or NF-κB signaling. Members of the endothelin system might be used as cancer biomarker and from a therapeutic point of view, targeting the endothelin axis is a promising aim. In effect, potential drugs may include endothelin converting enzyme inhibitors as well as selective and non-selective antagonists of endothelin receptor types A and B. Biomedical Reviews 2014; 25: 1-13.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"39 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83006379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The aim of this review is to appraise the usage of a newly approved anti-vascular endothelial growth factor (anti-VEGF) fusion protein, aflibercept, in ocular neovascular disorders such as diabetic retinopathy and age-related macular degeneration. Aflibercept is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the risk for immunogenicity in human patients. In this short review we investigate the available literature and data from clinical studies on the efficacy, pharmaceutical and pharmacological properties of aflibercept, and identify its possible advantages over commercially available anti-VEGF drugs. Biomedical Reviews 2014; 25: 59-65.
{"title":"NEW APPROACH IN THE TREATMENT OF OPHTHALMIC NEOVASCULAR DISORDERS: USING FUSION PROTEIN AFLIBERCEPT","authors":"K. Georgiev, Dobrin D. Georgiev, D. Georgiev","doi":"10.14748/BMR.V25.1048","DOIUrl":"https://doi.org/10.14748/BMR.V25.1048","url":null,"abstract":"The aim of this review is to appraise the usage of a newly approved anti-vascular endothelial growth factor (anti-VEGF) fusion protein, aflibercept, in ocular neovascular disorders such as diabetic retinopathy and age-related macular degeneration. Aflibercept is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the risk for immunogenicity in human patients. In this short review we investigate the available literature and data from clinical studies on the efficacy, pharmaceutical and pharmacological properties of aflibercept, and identify its possible advantages over commercially available anti-VEGF drugs. Biomedical Reviews 2014; 25: 59-65.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"3 1","pages":"59-65"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80675237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Over the past few decades, nanotechnology has emerged as a topic of great interest with a wide range of scientific investigations. This highly sophisticated technology covers a vast array of materials and devices including the high-resolution imaging for the early diagnosis of diseases and targeted delivery of genes or drugs leading to a more efficient therapeutic outcome. The limited efficacy of currently available therapeutic options against the neurological disorders have evoked tremendous efforts towards the development of novel treatment strategies. In this respect, multifunctional nanoparticles for targeted delivery of drugs across the blood-brain barrier have been designed to improve the bioavailability and reduce the side effects. Nanoengineered materials or nanodevices with ability to interact with biological systems including the nervous system have been designed for tracking the real-time dynamics of receptors in the central nervous system as well as neuronal recording or stimulation that may result in the neuroprotection or neural regeneration. Indeed, application of the cutting-edge nanotechnologies may revolutionize our knowledge about the neurophysiology and neurobiology including the cellular or molecular events in neurons leading to the more efficient treatments in central nervous system disorders. In the present article, an overview of the theranostic (therapeutic and diagnostic) potential of nanopharmaceuticals in the neurological disorders has been provided. Biomedical Reviews 2014; 25: 25-34.
{"title":"Nanopharmaceuticals: Innovative theranostics for the neurological disorders","authors":"P. Hassanzadeh","doi":"10.14748/BMR.V25.1043","DOIUrl":"https://doi.org/10.14748/BMR.V25.1043","url":null,"abstract":"Over the past few decades, nanotechnology has emerged as a topic of great interest with a wide range of scientific investigations. This highly sophisticated technology covers a vast array of materials and devices including the high-resolution imaging for the early diagnosis of diseases and targeted delivery of genes or drugs leading to a more efficient therapeutic outcome. The limited efficacy of currently available therapeutic options against the neurological disorders have evoked tremendous efforts towards the development of novel treatment strategies. In this respect, multifunctional nanoparticles for targeted delivery of drugs across the blood-brain barrier have been designed to improve the bioavailability and reduce the side effects. Nanoengineered materials or nanodevices with ability to interact with biological systems including the nervous system have been designed for tracking the real-time dynamics of receptors in the central nervous system as well as neuronal recording or stimulation that may result in the neuroprotection or neural regeneration. Indeed, application of the cutting-edge nanotechnologies may revolutionize our knowledge about the neurophysiology and neurobiology including the cellular or molecular events in neurons leading to the more efficient treatments in central nervous system disorders. In the present article, an overview of the theranostic (therapeutic and diagnostic) potential of nanopharmaceuticals in the neurological disorders has been provided. Biomedical Reviews 2014; 25: 25-34.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"9 1","pages":"25-34"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90102688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The membrane flow of eukaryotic cells occurs through vesicles that bud from a donor compartment, move and fuse with an acceptor compartment. Rab (Ras-related in brain), which belong to the Ras superfamily of small GTPases, emerged as a central player of vesicle mobility in both secretory and endocytic pathway, Rab7a being a master regulator of late endocytic trafficking. Elucidation of how mutant or dysregulated Rab7 GTPase and accessory proteins contribute to organ specific and systemic disease remains an area of intensive study and an essential foundation for effective drug targeting. Mutation of Rab7 or associated regulatory proteins causes numerous human genetic diseases. Cancer and neurodegeneration represent examples of acquired human diseases resulting from the up- or down-regulation or aberrant function of Rab7. The broad range of physiologic processes affected by altered Rab7 activity is based on its pivotal roles in membrane trafficking and signaling. The Rab7-regulated processes of cargo sorting, cytoskeletal translocation of vesicles and appropriate docking and fusion with the target membranes control cell metabolism, growth and differentiation. In this review, role of Rab7 in endocytosis is evaluated to illustrate normal function and the consequences of dysregulation resulting in human disease. Selected examples are designed to illustrate how defects in Rab7 activity alter endocytic trafficking that underlie neurologic, lipid storage, and bone disorders as well as cancer. Biomedical Reviews 2014; 25: 67-81.
{"title":"RAB7A: THE MASTER REGULATOR OF VESICULAR TRAFFICKING","authors":"Soumik Basuray","doi":"10.14748/BMR.V25.1049","DOIUrl":"https://doi.org/10.14748/BMR.V25.1049","url":null,"abstract":"The membrane flow of eukaryotic cells occurs through vesicles that bud from a donor compartment, move and fuse with an acceptor compartment. Rab (Ras-related in brain), which belong to the Ras superfamily of small GTPases, emerged as a central player of vesicle mobility in both secretory and endocytic pathway, Rab7a being a master regulator of late endocytic trafficking. Elucidation of how mutant or dysregulated Rab7 GTPase and accessory proteins contribute to organ specific and systemic disease remains an area of intensive study and an essential foundation for effective drug targeting. Mutation of Rab7 or associated regulatory proteins causes numerous human genetic diseases. Cancer and neurodegeneration represent examples of acquired human diseases resulting from the up- or down-regulation or aberrant function of Rab7. The broad range of physiologic processes affected by altered Rab7 activity is based on its pivotal roles in membrane trafficking and signaling. The Rab7-regulated processes of cargo sorting, cytoskeletal translocation of vesicles and appropriate docking and fusion with the target membranes control cell metabolism, growth and differentiation. In this review, role of Rab7 in endocytosis is evaluated to illustrate normal function and the consequences of dysregulation resulting in human disease. Selected examples are designed to illustrate how defects in Rab7 activity alter endocytic trafficking that underlie neurologic, lipid storage, and bone disorders as well as cancer. Biomedical Reviews 2014; 25: 67-81.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"110 1","pages":"67-81"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75985604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and understanding the molecular changes associated with EOC etiology could lead to the identification of novel targets for more effective therapeutic interventions. Glycosylation represents a post-translational modification (PTM) of proteins playing a major role in various cellular functions. Moreover, glycosylation participates in major pathobiological events during tumor progression, as aberrant expression of glycan structures has been shown to contribute in alterations of specific cellular onco-phenotypes, including tumor cell proliferation, migration and invasion. This review aims to describe what is currently known about aberrant glycosylation in EOC, and more specifically, the contribution of aberrant O-linked glycosylation in EOC progression. We also discuss our findings about the altered GALNT3 overexpression in EOC and its involvement in disease dissemination through aberrant mucin O-glycosylation, as well as the potential to exploit the role of GALNT3 in understanding the general mechanisms of abnormal glycosylation implicated in EOC spreading. Further analyses in cancer glycobiology could significantly enhance our understanding of the molecular mechanisms of cancer progression, including EOC dissemination, and could lead to the identification of novel biomarkers/therapeutic targets for better management of this deadly disease. Biomedical Reviews 2014; 25: 83-92.
{"title":"Role of aberrant glycosylation in ovarian cancer dissemination","authors":"Razan Sheta, D. Bachvarov","doi":"10.14748/BMR.V25.1050","DOIUrl":"https://doi.org/10.14748/BMR.V25.1050","url":null,"abstract":"Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and understanding the molecular changes associated with EOC etiology could lead to the identification of novel targets for more effective therapeutic interventions. Glycosylation represents a post-translational modification (PTM) of proteins playing a major role in various cellular functions. Moreover, glycosylation participates in major pathobiological events during tumor progression, as aberrant expression of glycan structures has been shown to contribute in alterations of specific cellular onco-phenotypes, including tumor cell proliferation, migration and invasion. This review aims to describe what is currently known about aberrant glycosylation in EOC, and more specifically, the contribution of aberrant O-linked glycosylation in EOC progression. We also discuss our findings about the altered GALNT3 overexpression in EOC and its involvement in disease dissemination through aberrant mucin O-glycosylation, as well as the potential to exploit the role of GALNT3 in understanding the general mechanisms of abnormal glycosylation implicated in EOC spreading. Further analyses in cancer glycobiology could significantly enhance our understanding of the molecular mechanisms of cancer progression, including EOC dissemination, and could lead to the identification of novel biomarkers/therapeutic targets for better management of this deadly disease. Biomedical Reviews 2014; 25: 83-92.","PeriodicalId":8906,"journal":{"name":"Biomedical Reviews","volume":"38 1","pages":"83-92"},"PeriodicalIF":0.0,"publicationDate":"2014-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82215032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：