Understanding PTMs in Neurodegenerative Diseases

Description

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 interested in delving into work with proteomic studies and PTMs.  Preface Contents Chapter 1: Protein Extraction and Sample Preparation Methods for Shotgun Proteomics with Central Nervous System Cells and Brain Tissue 1.1 Introduction 1.2 Lysis Buffers 1.3 Buffer Compositions, Pros, and Cons 1.3.1 RIPA Buffer 1.3.2 Modified RIPA Buffer 1.3.3 SDS Sample Buffer 1.3.4 NP-40 Lysis Buffer 1.3.5 HEPES Lysis Buffer 1.3.6 CHAPS Lysis Buffer 1.3.7 Urea Buffer 1.3.8 Protease Inhibitor Cocktail 1.4 Sample Preparation Methods 1.4.1 Central Nervous System (CNS) Cells 1.4.2 Postmortem Brain Tissue 1.4.3 Cerebrospinal Fluid (CSF) 1.5 Digestion Methods for Shotgun Proteomics 1.5.1 In-Solution Digestion 1.5.2 Homemade C18 Microcolumn 1.5.3 Filter-Aided Sample Preparation (FASP) 1.5.4 Suspension Trap (S-TRAP) 1.6 Conclusions References Chapter 2: Phosphopeptide Enrichment Techniques: A Pivotal Step for Phosphoproteomic Studies 2.1 Introduction 2.2 Phosphopeptide Enrichment 2.3 IMAC 2.4 TiO2 2.5 TiO2 Micro-Column 2.6 SIMAC 2.7 Conclusion References Chapter 3: Post-Translational Modifications During Brain Development 3.1 Biological Steps of Neurodevelopment and Post-translational Modifications 3.2 Post-translational Modifications During Neurodevelopment 3.2.1 Cytoskeletal Proteins 3.2.2 Gene Transcription and Protein Translation 3.2.3 Signaling Pathways 3.3 Concluding Remarks References Chapter 4: Aberrant Protein Glycosylation in Brain Cancers, with Emphasis on Glioblastoma 4.1 Introduction 4.2 Asparagine N-Linked Glycosylation Family (ALG) 4.3 β-1,4-Galactosyltransferase (B4T) and β-1,3-Nacetylglucosaminyltransferase (B3T) Families 4.4 Fucosyltransferase Family (FUT) 4.5 N-Acetylgalactosaminyltransferase Family (GALNT) 4.6 Hexosaminidase Family (HEX) 4.7 Mannosidase Family (MAN) 4.8 N-Acetylglucosaminyltransferase Family (MGAT) 4.9 Sialidase Family (NEU) 4.10 Solute Carrier 35 Family (SLC35) 4.11 Sialyltransferase Family (ST) 4.12 Conclusions and Outlook References Chapter 5: Post-translational Modification in Muscular Dystrophies 5.1 Introduction 5.2 PTMs and Duchenne Muscular Dystrophy 5.3 Glycosylation of α-Dystroglycan in MDs 5.4 PTMs and Other Muscular Dystrophies 5.5 Muscular Dystrophy Treatments and PTMs 5.6 Conclusions References Chapter 6: Post-translational Modifications in Parkinson’s Disease 6.1 Parkinson’s Disease 6.1.1 Alpha-Synuclein Aggregation and Parkinson’s Disease 6.1.2 Mitochondrial Dysfunction and Parkinson’s Disease 6.2 Post-translational Modifications 6.2.1 Phosphorylation 6.2.2 Glycosylation 6.2.3 Acetylation 6.2.4 Ubiquitination 6.3 Mass Spectrometry in the Investigation of PTMs 6.4 PTMs and PD 6.4.1 Phosphorylation 6.4.2 Ubiquitination 6.4.3 Glycosylation 6.5 Conclusion References Chapter 7: Histone Modifications in Neurological Disorders 7.1 Histones and Their Modifications 7.2 Investigating Histone PTMs 7.3 Specific Roles in Neurological Disorders 7.3.1 Alzheimer’s, Parkinson’s, and Huntington’s Diseases 7.4 Aging and Cognitive Decline 7.5 Cognition, Memory, and Neurodevelopment 7.6 Schizophrenia and Bipolar Disorder 7.7 Depression and Chronic Stress 7.8 Concluding Remarks References Chapter 8: Mitochondrial Dysregulation and the Influence in Neurodegenerative Diseases 8.1 Introduction 8.2 Neurodegenerative Diseases and Evidence of Mitochondrial Dysfunction 8.2.1 Parkinson’s Disease 8.2.2 Alzheimer’s Disease 8.2.3 Huntington’s Disease 8.2.4 Amyotrophic Lateral Sclerosis 8.3 Concluding Remarks References Chapter 9: PTMs: A Missing Piece for Schizophrenia Studies 9.1 Introduction 9.2 PTMs in the Pathophysiology of Schizophrenia 9.2.1 Phosphorylation 9.2.2 Glycosylation 9.2.3 Ubiquitination 9.2.4 Palmitoylation 9.3 Future Directions and Concluding Remarks References Chapter 10: Post-translational Modifications in Brain Diseases: A Future for Biomarkers 10.1 Introduction 10.2 PTM Types 10.3 Regulation 10.4 PTMs in Brain Diseases 10.4.1 Neurodegenerative Disorders 10.4.2 Psychiatric Disorders 10.4.3 Aging and Cancer 10.5 Biomarker Sources 10.6 Concluding Remarks References Index