Neuroprotection in Autism, Schizophrenia and Alzheimer's Disease

Description

Neuroprotection in Autism, Schizophrenia and Alzheimer's Disease provides an up-to-date overview on recent clinical studies and the similarities discovered in the most prevalent brain disorders. The book's content will help shed light on basic mechanisms and provide new avenues for early diagnosis toward disease prevention and disease modification. It is written for researchers, clinicians and medical physicians in neuroscience, neurology and psychiatry. Sections discuss the shared pathophysiological mechanisms that underlie autism, schizophrenia/mood disorders and Alzheimer’s disease, i.e. neurodevelopmental disorders, neuropsychiatric diseases and neurodegenerative disorders. Offers an up-to-date overview of basic and clinical studies concerning similarities in the most prevalent brain disordersHelps the reader become familiar with novel neuroprotective mechanisms and experimental treatment modalities in these difficult to treat disordersWritten for researchers, clinicians and medical physicians in neuroscience, neurology and psychiatry Cover NEUROPROTECTION IN AUTISM, SCHIZOPHRENIA AND ALZHEIMER’S DISEASE Copyright Contributors About the editors Introduction Acknowledgments Conflict of interest Section I: Overview 1 Activity-dependent neuroprotective protein (ADNP)/NAP (CP201): Autism, schizophrenia, and Alzheimer’s disease Introductory remarks: Activity-dependent neuroprotective protein (ADNP) discovery through vasoactive intestinal peptide (VI ... ADNP macromolecular interactions The ADNP syndrome in patients and models: A CP201 (NAP) connection Additional problems (selected) The schizophrenia connection The Alzheimer’s disease (AD) connection Epilogue: Autism, schizophrenia, and AD shared mechanism through the ADNP prism Selected Internet resources Acknowledgments Conflict of interest References 2 Clinical convergence of autism, schizophrenia, and Alzheimer’s disease: The case of social cognition Introduction Clinical characteristics and symptomatology of schizophrenia, ASD, and Alzheimer’s disease Clinical convergence of schizophrenia, Alzheimer's disease and ASD Social cognition Social cognition and ASD Metaanalyses of ASD subjects in general Metaanalysis of subjects with specific genetic diagnosis of ASD Metaanalyses comparing ASD with schizophrenia Metaanalysis comparing ASD with ADHD Metaanalyses of studies detecting brain areas associated with given domains of social cognition in ASD Social cognition and schizophrenia Metaanalysis of social cognition domains in high risk groups for psychosis Metaanalysis of social cognition domains in first-degree relatives of people with schizophrenia Metaanalysis of social cognition domains and processes in schizophrenia subjects Metaanalysis on the relationship between neurocognition and social cognition with functional outcomes in nonaffective psych ... Metaanalyses comparing social cognition domains and processes between schizophrenia and ASD Metaanalysis comparing social cognition domains and processes between schizophrenia and bipolar disorder Metaanalyses of studies detecting brain areas associated with given domains of social cognition in schizophrenia Social cognition and Alzheimer’s disease Pharmacological treatment of social cognition impairments Oxytocin: A candidate treatment for dysfunctional social cognition Oxytocin treatment in ASD Oxytocin treatment in schizophrenia Pharmacological agents affecting the NMDA glutamate receptor as candidate treatments for dysfunctional social cognition Psychostimulant and other drugs as candidate treatments for dysfunctional social cognition Noninvasive brain stimulation techniques Perspective as to future modes of treatment targeting dysfunctional domains of social cognition References Section II: Autism 3 A contemporary view on the molecular basis of neurodevelopmental disorders Neurodevelopmental disorders Intellectual disability/intellectual development disorder (ID/IDD) Autism spectrum disorders (ASD) Attention-deficit hyperactivity disorder (ADHD) Other neurodevelopmental disorders Schizophrenia spectrum Bipolar disorders Epilepsy Genetic causes of NDDs Aneuploidies Repeat expansions Structural variation Copy number variation in NDDs Molecular mechanisms underlying CNVs NHAR-induced CNVs CNV syndromes due to nonhomology-driven mechanisms Triplications Complex structural variants Single-gene defects SNV categories Mutational effects Distinguishing variants from mutations Gene identification strategies Convergence to overlapping networks Gene networks in neurodevelopmental disorders From disease to networks From networks to disease References 4 Autism spectrum disorder: A clinical path to early diagnosis, evaluation, and intervention Diagnosis Evaluation of ASD in infancy Recognition of signs and symptoms neurodevelopmental workup Early diagnosis Developmental evaluation during first 6  months Developmental evaluation up to the first year and transition to second year (see Table 4.2) Atypical behaviors Parental concern and age of diagnosis Additional early differences and studies in progress About the “red flags” Etiology Diagnostic methods We suggest a stepwise approach (see flowchart) Comprehensive evaluation and planning of treatment ( Chart 4.1) Treatment and intervention The significance of early diagnosis Summary of Challenges Acknowledgment References 5 Neuroinflammation and neuroprotection in schizophrenia and autism spectrum disorder Part ISchizophrenia Microglia Cytokines Oxidative stress Bdnf References Part IIAutism spectrum disorder (ASD) Microglial dysfunction in ASD Cytokine alterations in ASD Immune-modulating drugs for ASD Brain-derived neurotropic factor (BDNF) dysregulation in ASD Oxidative stress in ASD References Section III: Neuropsychiatric disorders 6 Neuroprotective roles of neurotrophic factors in depression Introduction The need for novel treatment strategies in depression Evidence suggestive of impaired neuroprotection and neurotrophic factors signaling in depression Altered brain volume, connectivity, and cellular atrophy in depression Impaired neurogenesis in depression Neuroinflammation and neurotoxicity in depression Altered neurotrophic factor signaling in depression Reduced levels of neurotrophic factors in individuals with depression Evidence from genetic studies supporting impaired neurotrophic factor signaling in depression Stress and stress-induced depression and neurotrophic factor signaling in mouse and rat models Evidence for enhanced neuroprotection as an underlying mechanism of current successful therapeutic strategies in depression Several antidepressant treatments have neuroprotective roles in depression Increased BDNF may be a mechanism of action contributing to the effect of antidepressants The potential of neurotrophic factors in disease-modifying therapies for mood disorders and beyond Acknowledgments References 7 Neuroprotective roles of neurotrophic growth factors in mood disorders Neurotrophic growth factors and their receptors Contributions of BDNF to the pathophysiology of mood disorders BDNF and other neurotrophin levels in major depressive disorder BDNF genetics in human major depressive disorder Do peripheral BDNF levels and BDNF genotype provide insight into MDD risk and/or antidepressant efficacy? Analysis of mouse models of the BDNF Val66Met polymorphism BDNF and NGF levels in mouse models of depression-like behavior Regulation of depression-like behavior by BDNF/TrkB and proBDNF/p75NTR signaling Regulation of antidepressant efficacy by BDNF expression Mechanisms by which BDNF and other neurotrophins regulate mood disorders and antidepressant efficacy Neuroprotective effects and the regulation of neurogenesis by BDNF and other neurotrophins Regulation of neuronal plasticity by BDNF Regulation of excitatory-inhibitory balance by BDNF Rapid-acting antidepressants regulate local translation and activity-dependent secretion of BDNF Targets of BDNF/TrkB signaling with potential roles in mood disorders Overview References 8 Heme metabolism, mitochondria, and complex I in neuropsychiatric disorders Introduction Heme Heme biosynthesis pathway Heme catabolic pathway Heme in neurons Alterations in heme metabolism in neuropsychiatric disorders Heme pyrrole ring as a marker for mental illness Alzheimer’s disease and the mitochondria Complex I and IV in Alzheimer’s disease Heme metabolism in Alzheimer’s disease Parkinson’s disease and the mitochondria Complex I and Parkinson’s disease Heme metabolism in Parkinson’s disease Schizophrenia and The mitochondria Complex I in schizophrenia Heme metabolism in schizophrenia Conclusions Acknowledgment References 9 Neuroprotective effects of lithium in neuropsychiatric disorders Introduction Lithium’s effect on autophagy, BDNF, inflammation, mitochondrial function and apoptosis Autophagy Bdnf Inflammation Mitochondria Apoptosis Lithium and neuropsychiatric disorders Preface Stroke Animal studies Human studies Huntington’s disease Nonhuman studies Human studies Alzheimer’s disease Tissue and animal studies Risk of Alzheimer’s disease in lithium users Human clinical studies Parkinson’s disease Studies in neuronal cells in culture Animal studies Human studies Fragile X syndrome Animal studies Drosophila Rodents Human studies Amyotrophic lateral sclerosis Nonhuman studies Human studies Lithium combined with another drug Lithium by its own Multiple sclerosis Animal studies Human studies Summary References Section IV: Alzheimer and neurodegenerative diseases 10 Tau-based therapies for Alzheimer’s disease: Promising novel neuroprotective approaches Introduction Modulators of tau posttranslational modifications Inhibitors of kinases that phosphorylate tau Inhibitors of tau acetylation Modulators of O -GlcNAcylation MT stabilizers Inhibitors of tau aggregation Immunotherapy Passive immunotherapy Anti-tau antibody therapies being investigated in clinical trials Active immunotherapy: Vaccination against tau Reduction of tau levels Concluding remarks and future directions References 11 Acetylation of tubulin: A feasible protective target from neurodevelopment to neurodegeneration Introduction The basis for tubulin code Acetylation of tubulin Acetylation of tubulin in neurodevelopmental disorders Autism spectrum disorders Schizophrenia Acetylation of tubulin in neurodegenerative diseases Alzheimer’s disease Parkinson’s disease Open questions and future perspective Acknowledgments References Index A B C D E F G H I J K L M N O P R S T U V W Z Back Cover