Neuroprotection in Autism, Schizophrenia and Alzheimer's Disease

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