书目名称 | Understanding PTMs in Neurodegenerative Diseases | 编辑 | Victor Corasolla Carregari | 视频video | http://file.papertrans.cn/942/941584/941584.mp4 | 概述 | Increases awareness of how PTMs may help researchers understand mechanisms in neurodegenerative diseases.Explains how proteomic studies of PTMs can be applied to neurodegenerative diseases and relevan | 丛书名称 | Advances in Experimental Medicine and Biology | 图书封面 |  | 描述 | This new volume, a part of the Proteomics, Metabolomics, Interactomics and Systems Biology series, will explain how proteomic studies of post-translational modifications (PTMs) can be applied to neurodegenerative diseases and relevant studies. The goal of the book is to increase awareness among researchers about how PTMs may be helpful in understanding mechanisms in various neurodegenerative diseases through proteomic studies. This book will serve as a tool for those who want to begin work in the proteomics field and explore how to implement PTMs studies into their work. Chapter authors will describe different PTMs enrichment methods developed by experts in the field so that researchers may learn to apply these methods and techniques to new studies. Divided into three sections, chapters will cover sample preparation, data quality, enrichment techniques, guidelines on how to analyze PTMs, and explain the role of PTMs and different brain diseases. Among those topics includes will be brain cancer, SLA disease, Parkinsons disease, muscular dystrophies, and schizophrenia. This volume will be useful for researchers and students studying brain and neurodegenerative diseases who are intere | 出版日期 | Book 2022 | 关键词 | proteomics; neurodegenerative diseases; Phosphopeptides; Glycopeptides; Acetylation; enrichment technique | 版次 | 1 | doi | https://doi.org/10.1007/978-3-031-05460-0 | isbn_ebook | 978-3-031-05460-0Series ISSN 0065-2598 Series E-ISSN 2214-8019 | issn_series | 0065-2598 | copyright | The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerl |
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Front Matter |
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Abstract
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,Protein Extraction and Sample Preparation Methods for Shotgun Proteomics with Central Nervous Syste |
Victor Corasolla Carregari |
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Abstract
Shotgun proteomics based in mass spectrometry has been extensively utilized to investigate biological samples for basic and applied research in the clinical field to elucidate changes in the molecular mechanisms caused by diseases. There is still a great lack of information about the molecular mechanisms and the origins of most brain disorders, which makes shotgun proteomics an interesting tool in the study of these diseases. A wide range of samples can be used to study such diseases, such as cerebrospinal fluid, central nervous system cells, and brain tissue via . analysis. As such, different protein extraction methods must be applied to achieve the best results for each sample type. The lysis buffer, digestion protocol, and peptide purification steps chosen prior to liquid chromatography-mass spectrometry analyses are essential to obtain reliable proteomic datasets. For this reason, the availability of a list with a variety of methods and a description of the pros and cons for each one has been compiled and elaborated upon. This review presents several methods for protein extraction, protein digestion, and sample cleanup with a focus on shotgun proteomics via mass spectrometry an
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,Phosphopeptide Enrichment Techniques: A Pivotal Step for Phosphoproteomic Studies, |
Victor Corasolla Carregari |
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Abstract
Many pathological conditions are caused by dysregulation of cell signaling, which can generate a cascade of abnormal responses and completely change the functions of a cell or tissue. A large portion of the regulation of these signals is via protein phosphorylation, in which cell responses can be activated or inhibited. Proteins that are both downstream and upstream of a phosphorylated protein can be modified, altering metabolism and other biological processes. Recently, the number of phosphoproteomic studies based on mass spectrometry has increased, constantly aiming to obtain a higher coverage of proteins and increase the number and location of their phospho-sites, as well as better understand their respective phosphorylation states. In this way, it is possible to better understand biological processes as a whole and their roles in cellular dysfunctions and diseases. To study changes at the phosphoproteome level, the stochiometric imbalance between the non-phosphorylated and phosphorylated peptides must be overcome, since higher quantities and comparatively better ionization of non-phosphorylated peptides can suppress the ion signals of the phosphorylated peptides. It is for this
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,Post-Translational Modifications During Brain Development, |
Bradley J. Smith,Victor Corasolla Carregari |
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Abstract
Several classes of post-translational modifications (PTMs) regulate various processes that occur during neurodevelopment. The first of these processes is the regulation of the cytoskeleton and cytoskeleton-associating proteins, responsible for the stability, reorganization, and binding of microtubules and actin filaments. Dysregulations in these PTMs lead to dysregulated brain volume and composition, structural defects, behavioral defects, and dendrite growth. The second class of processes involves gene regulation, from chromatin modulation to protein turnover and degradation. Proper gene expression during neurodevelopment is critical to ensure correctly matured cells; dysregulation of PTMs in these pathways leads to various altered morphological and behavioral phenotypes. The third class of processes that are affected by PTMs is cell signaling and signal transduction, vital to cell migration and axonal guidance. Neurodevelopment is a complex sequence of spatially and temporally regulated processes, and PTMs play important roles in this regulation. Most of the known modifications have yet to be studied in depth and much remains undiscovered about their roles in neurodevelopment and
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,Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma, |
Livia Rosa-Fernandes,Sueli Mieko Oba-Shinjo,Janaina Macedo-da-Silva,Suely Kazue Nagahashi Marie,Gius |
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Abstract
Aberrant glycosylation has been associated with several processes of tumorigenesis from cell signaling, migration and invasion, to immune regulation and metastasis formation. The biosynthesis of glycoconjugates is regulated through concerted and finely tuned enzymatic reactions. This includes the levels and activity of glycosyltransferases and glycosidases, nucleotide sugar metabolism, substrate availability, epigenetic condition, and cellular functional state. Glioblastoma (GBM) is the most aggressive brain tumor, frequently occurring in adults with overall survival not surpassing 17 months after diagnosis. GBM has been classified by the World Health Organization (WHO) as a grade 4 astrocytoma and stratified into G-CIMP, proneural, classical, and mesenchymal subtypes. Several biomolecular features associated with GBM aggressiveness have been elucidated; however, more studies are needed to elucidate the role of glycosylation in GBM pathology, looking at their potential as cancer targets. Here, we focus on the alteration of genes involved in protein N- and O-linked glycosylation in GBM. Specifically, the mRNA levels of glycogenes were analyzed using astrocytoma-TCGA-RNAseq datasets
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,Post-translational Modification in Muscular Dystrophies, |
Martina Sandonà,Valentina Saccone |
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Abstract
Muscular dystrophies are a complex group of inherited neuromuscular disorders that progressively lead to a loss of muscle fibers and mobility and muscle weakness; over time, they evolve to an increasing level of disability. Muscular dystrophies are mostly caused by genetic mutations in proteins responsible for maintaining sarcolemma structures, such as an absence or reductions of dystrophin expression, conditions which are strictly related to muscular disorders that affect most people with this disease. Along the years, with the recent advances in the understanding of muscular dystrophies, it has been shown that many changes in Post-Translational Modifications (PTMs) of muscle proteins are associated with muscular dystrophies, wherein pathogenic alterations in the modulation of these muscle proteins are directly related to the incidence of this disease. An increase in the identification of the genetic bases and molecular mechanisms involved in the most common form of muscular dystrophies, including PTMs changes, holds potential to develop new therapeutic approaches. In this chapter we will describe the most common muscular dystrophies and changes in PTM processes such as phosphoryl
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,Post-translational Modifications in Parkinson’s Disease, |
André Saraiva Leão Marcelo Antunes |
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Abstract
Parkinson’s disease (PD) is a complex neurodegenerative disorder characterised by progressive degeneration of the dopaminergic neurons in the substantia nigra leading to severe motor complications. The etiology of the disease is unknown with its sporadic form accounting for 90% of cases. To date, over 20 genes have been identified as the cause of the inherited form of PD, many of them linked to the protein alpha-synuclein and mitochondrial function. Post-translational modifications of proteins allow cells to dynamically control signalling networks and diversify protein functions. This chapter will discuss briefly the main types of post-translational modifications, how to study them and how they affect proteins involved in PD.
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,Histone Modifications in Neurological Disorders, |
Bradley J. Smith,Victor Corasolla Carregari |
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Abstract
Post-translational modifications (PTMs) have a strong impact on many proteins across all kingdoms of life, affecting multiple functional and chemical properties of their protein recipients. With increasing knowledge about their functions, targets, and biological effects, dysregulations in PTMs have been implicated in various dysfunctions and diseases. One such target are histones, which compose the majority of the protein component of chromatin and the modulation of the 30+ PTMs that are known to affect them can have profound effects on chromatin state, gene expression, and DNA repair. In this review, the histone targets of PTMs are compiled in the context of neurological disorders, highlighting their specific biological roles and any previously implicated dysregulations in several classes of brain disease. Better understanding the pathogenic dysregulations of PTMs in such disorders can help to better understand their causes, as well as open doors to new possibilities for biomarkers and therapeutic targets.
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,Mitochondrial Dysregulation and the Influence in Neurodegenerative Diseases, |
Giuliana S. Zuccoli,Victor Corasolla Carregari |
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Abstract
Mitochondrial function is essential to ensure vital cellular processes. Given the energy requirement of the brain, neuronal function, viability, and survival are closely related to proper mitochondrial function. Dysregulation of mitochondrial processes can lead to several detrimental effects in the cells and stablish the condition of mitochondrial dysfunction. This dysfunction is proposed to be greatly implicated in several neurodegenerative diseases, with evidence of compromised mitochondrial function and dynamics in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.
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,PTMs: A Missing Piece for Schizophrenia Studies, |
Caroline Brandão-Teles,Bradley J. Smith,Victor Corasolla Carregari |
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Abstract
One of the closest regulatory mechanisms to a cellular phenotype is post-translational modifications (PTMs), a diverse class of changes that proteins can undergo to change various physical and functional properties. PTMs hold great potential to better understand multifactorial diseases and disorders like schizophrenia. The field of PTMomics is still expanding and developing, though several modifications have already been implicated in the etiology and treatment of schizophrenia. Nonetheless, much has yet to be uncovered due to the vast number of modifications that occur on proteins. Here, some of the most well-supported arguments for PTM dysregulation in schizophrenia are raised, leaving the door open for multiple other modifications and their potential.
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,Post-translational Modifications in Brain Diseases: A Future for Biomarkers, |
Licia C. Silva-Costa,Bradley J. Smith |
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Abstract
Several omic fields have been used in the development of biomarker panels, most traditionally involving genetics and proteomics. The post-translational modification of proteins, however, is an important regulatory system of many biological processes, affecting a wide range of biochemical properties of proteins, including their binding, localization, activity, and stability. These modifications are not analyzed if not specifically searched for in proteomic workflows, making them an underrepresented source of important information in the field of biomarker research. Biomarkers can particularly benefit the diagnosis and prognosis of neurological and psychiatric diseases due to the difficulty of accessing tissue and distinguishing between multiple possible conditions. In this article, post-translational modifications in the context of brain disease are compiled, highlighting the potential that this data source holds for improving the field of medicine.
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Back Matter |
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Abstract
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