Proteins Associated with Neurodevelopmental Disorders (Nutritional Neurosciences)

Description

This book comprehensively reviews the proteins associated with neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). It also discusses the interactions of the associated-proteins, like bromodomain-containing proteins (BCPs), kinases, synaptic proteins, scaffolding proteins, transcriptional factors, and DNA-binding proteins at the subcellular and molecular levels. The book also explores the potential of these proteins as a druggable target and a biomarker in the neurodevelopmental disorders. The book further explores the recent advancements in understanding the important role of epigenetic factors in predisposition to these diseases. Lastly, it presents genetic factors that lead to variation in gene expression in these diseases, disorders management via diet intervention and the future potential of stem cell therapy. Preface Acknowledgments Contents Editors and Contributors 1: Principal Molecular Pathways Affected in Autism Spectrum Disorder 1.1 Introduction 1.2 Principal Signaling Pathways 1.2.1 Altered WNT Signaling in ASD 1.3 Genetic Etiologies 1.4 Modulators and Effectors of WNT Signaling in ASD Etiology 1.5 Altered Sonic Hedgehog (SHH) Signaling in ASD 1.6 Altered Retinoic Acid (RA) Signaling in ASD 1.7 Altered Fibroblast Growth Factor (FGF) Signaling in ASD 1.8 Altered TGF-β/BMP Signaling in ASD 1.9 Signaling Crosstalk in ASD 1.10 Nongenetic ASD Etiologies 1.11 Advancing Paternal Age 1.12 Viral Infection 1.13 Valproic Acid (VPA) 1.14 Precision Medicine Approaches in ASD 1.15 Future Perspectives and Conclusions References 2: Genes and Specific (Related) Proteins in Neurodevelopmental Disorders 2.1 Background 2.2 Genes Involved in Different NDDs 2.2.1 Autism Spectrum Disorder (ASD) 2.2.2 Attention-Deficit Hyperactivity Disorder (ADHD) 2.2.3 Intellectual Disability (ID) 2.2.4 Dyslexia 2.2.5 Tourette´s Syndrome (TS) 2.3 Proteins Associated with NDDs 2.4 Signaling Pathways Involved in NDDs 2.4.1 Autism Spectrum Disorder (ASD) 2.4.2 Attention-Deficit Hyperactivity Disorder (ADHD) 2.4.3 Intellectual Disability (ID) 2.4.4 Dyslexia 2.4.5 Tourette´s Syndrome (TS) 2.5 Conclusions References 3: Neurodevelopmental Disorders: Epigenetic Implications and Potential Analysis Methods 3.1 Introduction 3.2 Epigenetics of Neurodevelopmental Disorders 3.3 ChIP-seq or Chromatin Immunoprecipitation and Sequencing 3.3.1 ChIP-seq Background 3.3.2 ChIP-seq Method Outline 3.3.2.1 Cross-Linking 3.3.2.2 Chromatin Fragmentation 3.3.2.3 Immunoprecipitation by Antibody 3.3.2.4 Immobilization on Beads 3.3.2.5 Analysis of ChIP Results 3.3.3 Modifications to ChIP 3.3.4 Application of ChIP-seq to Study Neurodevelopmental Disorders 3.4 RIME or Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins 3.4.1 RIME Background 3.4.2 RIME Method Outline 3.4.2.1 RIME Data Analysis 3.4.3 Expansion of RIME Methodology 3.4.4 Application of RIME to Study Neurodevelopmental Disorders 3.5 CUT&Tag or Cleavage Under Targets and Tagmentation 3.5.1 CUT&Tag Background 3.5.2 CUT&Tag Method Outline 3.5.3 Application of CUT&Tag to Study Neurodevelopmental Disorders 3.5.4 Single-Cell CUT&Tag 3.6 ATAC-seq or Assay for Transposase-Accessible Chromatin with High-Throughput Sequencing 3.6.1 ATAC-seq Background 3.6.2 ATAC-seq Method Outline 3.6.3 Single-Cell ATAC-seq 3.6.4 Application of ATAC-Seq to Study Neurodevelopmental Disorders 3.7 Conclusions References 4: Methionine Is a Major Methyl Donor Whose Dietary Intake Likely Plays a Causative Role for Neurodevelopmental Disorders via ... 4.1 Introduction 4.2 Epigenomic Regulation and CH3 4.2.1 DNA Methylation and Hydroxymethylation 4.2.2 Histone Methylation 4.3 The MMC and CH3 4.4 Disruption of the Methionine Cycle Due to Genetic Defects Leads to ND 4.4.1 MTR and MTRR 4.4.2 MTHFR 4.4.3 SIRT1 4.4.4 Hypermethioninemia Reported to Cause Neurological Disease 4.4.5 Mitochondrial DNA Depletion Disrupts the Methionine Cycle 4.5 Several NDs Show Aberrant and Even Diagnostic Methylation Epigenome Profiles 4.6 Nutritional Deficiency of Major Methyl Donors Impacts ND Causation 4.6.1 During Fetal, Pre-, Peri-, and Postnatal Development 4.6.2 During Childhood 4.7 Therapeutic and Prophylactic Use of Methionine for ND 4.7.1 Methionine Supplementation 4.7.2 Methionine Restriction 4.8 Conclusion References 5: Attention-Deficit Hyperactivity Disorder: Genetic, Pharmacogenetic, and Metabolomic Insights 5.1 Introduction 5.2 Genetic Insights in ADHD 5.2.1 Genes Linked to Anatomical Brain Alterations 5.2.2 Genes Linked to White Matter Brain Alterations 5.2.3 Genes Linked to Functional Brain Alterations 5.3 Pharmacogenetic Insights in ADHD 5.4 Metabolomic Insights in ADHD 5.5 Current Challenges and Future Perspective 5.6 Conclusions References 6: Genomic Profiling of ADHD 6.1 Introduction 6.2 Genetic Overlap 6.3 Psychiatric Comorbidity 6.4 Genetic Linkage Studies 6.5 Candidate Gene Association Studies 6.6 Genome-Wide Significant Common Variants 6.7 Common Variant ADHD as a Polygenic Disorder 6.8 Rare Variants and Genetic Syndromes 6.9 Diagnosis and Therapeutic Approaches to ADHD 6.10 Future Directions in Genetics Research 6.11 Conclusions References 7: The Role of Protein Kinases in the Cause and Progression of Attention-Deficit Hyperactivity Disorder 7.1 Introduction 7.2 Classification of Protein Kinases 7.3 Protein Kinases A, G, C 7.4 CaMKII 7.5 Casein Kinase 1 7.6 Cyclin-Dependent Kinase 5 7.7 MAPK 7.8 GSK-3β/Akt/mTOR/Wnt Signaling Pathways 7.9 ERK 7.10 TGF 7.11 Tyrosine Kinase 7.12 Conclusions References 8: Autism Spectrum Disorder (ASD) and Diet 8.1 Introduction 8.2 Epidemiology 8.3 Etiology 8.4 Metabolic Profiles in ASD 8.5 Diagnosis 8.6 DSM-5 Autism Spectrum Criteria 8.7 Clinical Characteristics 8.8 Associated Clinical Features 8.9 Evaluation 8.10 Treatment/Management 8.11 The Opioid Theory for ASD and Gluten- and Casein-Free Diet 8.12 Potential Side Effects of GF-CF Diet in ASD 8.13 Nutritional Supplements 8.14 Pharmacological Therapy 8.15 Novel Dietary Approaches 8.16 Conclusions References 9: Therapeutic Approaches for Attention Deficit-Hyperactivity Disorder 9.1 Introduction 9.2 Anatomical Changes in ADHD 9.3 Neurobiology of ADHD 9.4 Dopaminergic Hypothesis 9.5 Serotoninergic Theory 9.6 Cholinergic Theory 9.7 Pharmaceutical Agents 9.8 Traditional Therapeutic Approaches 9.8.1 Ayurveda 9.8.2 Herbs 9.8.3 Siddha 9.9 Traditional Chinese Medicines (TCM) 9.9.1 Chinese Herbal Medicine (CHM) 9.9.2 Acupuncture 9.9.3 Tuina (Chinese Medical Massage) 9.9.4 Tai chi chuan (Breathing and Exercise) 9.10 Nutritional Supplements 9.10.1 Vitamins 9.10.2 Minerals 9.10.3 Amino Acids 9.10.4 Essential Fatty Acids 9.11 Conclusions References 10: Influence of Amino Acids on Autism and Attention-Deficit Hyperactive Disorder 10.1 Autism: An Introduction 10.2 Impact of Amino Acids on Autism 10.2.1 Glutamate 10.2.2 d-Serine 10.2.3 Glycine 10.2.4 Gamma-Aminobutyric Acid (GABA) 10.2.5 Glutamine 10.2.6 Tryptophan 10.2.7 Taurine 10.2.8 Other Amino Acids 10.3 The Many Pathways Affected by Amino Acid Imbalance in the Brain 10.4 The Interaction Between Amino Acids and the Gut Microbiome in Relation to Autism 10.5 Attention-Deficit Hyperactivity Disorder 10.6 Impact of Amino Acids on ADHD 10.7 Conclusions References 11: Autism and the Scaffolding Protein Neurobeachin 11.1 Introduction 11.2 Scaffolding Proteins 11.3 BEACH Domain-Containing Proteins 11.4 Neurobeachin 11.5 Neurobeachin, an Autism Candidate Protein 11.6 Neurobeachin Studies in Animal Models 11.7 Functions of Neurobeachin 11.8 Lysosomal Trafficking Regulator Protein (LYST) 11.9 WDFY3 and WDFY4 11.10 Neurobeachin-Like 1 and Neurobeachin-Like 2 11.11 Conclusions References 12: Regulatory Role of ADGRL3, PARK2, and CNTNAP2 in Neurodevelopmental Disorders 12.1 Latrophilin 3/Adhesion G Protein-Coupled Receptor L3 (LPHN3/ADGRL3) 12.2 Parkin RBR E3 Ubiquitin Protein Ligase (PARK2) 12.3 Contactin-Associated Protein-Like 2 (CNTNAP2) 12.4 Conclusions References 13: Essential Role of nSR100 and CPEB4 Proteins During the Development of the Nervous System 13.1 Introduction 13.2 Regulation Through CPEB Proteins 13.3 Properties of CPEB Proteins 13.4 CPEB Proteins in the Development of the Nervous System 13.5 CPEB Role in Memory 13.6 CPEB Proteins in Disease 13.7 nSR100 Role in the Development of the Nervous System 13.8 nSR in Pathology 13.9 nSR100 and CPEB in Autism 13.10 Conclusions References 14: Current Trends of Stem Cells in Neurodegenerative Diseases 14.1 Introduction 14.1.1 Alzheimer´s Disease (AD) 14.1.2 Parkinson´s Disease (PD) 14.1.3 Amyotrophic Lateral Sclerosis (ALS) 14.1.4 Huntington´s Disease (HD) 14.1.5 Autism Spectrum and Neurodevelopmental Disorders 14.2 Stem Cells 14.2.1 Stem Cell Sources 14.3 Clinical Trials for Stem Cell Therapies 14.3.1 Human Embryonic Stem Cells 14.3.2 Induced Pluripotent Stem Cells 14.3.3 Bone Marrow and Umbilical Cord Stem Cells 14.3.4 Human Spinal Cord Stem Cells 14.3.5 Human Mesenchymal Stem Cells 14.4 Clinical Trials in the Context of Neurodegenerative Diseases 14.4.1 Clinical Trials for Alzheimer´s Disease 14.4.2 Clinical Trials for Parkinson´s Disease 14.4.3 Clinical Trials for Amyotrophic Lateral Sclerosis (ALS) 14.4.4 Clinical Trials for Huntington´s Disease 14.4.5 Clinical Trials for Autism Spectrum Neurodevelopmental Disorders 14.5 Conclusions References