Chapter 1: The multitude of therapeutic targets in neurodegenerative proteinopathies
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Abstract
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Protein Misfolding and Aggregation
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Mechanism of Assembly
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Prion-Like Propagation of Protein Assemblies
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Propagation Routes of Pathogenic Protein Aggregates
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Limiting Steps in the Propagation of Pathogenic Protein Assemblies
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Therapeutic Strategies Targeting the Physiological Levels of Aggregation-Prone Proteins Involved in Neurodegeneration
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Therapeutic Strategies Targeting the Misfolding and Aggregation of Proteins Involved in Neurodegeneration
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Therapeutic Strategies Targeting the Accumulation of Misfolded Pathologic Protein Aggregates
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Therapeutic Strategies Targeting the Cell-to-Cell Propagation of Pathogenic Protein Aggregates
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Therapeutic Strategies Aimed at Restoring the Damage Pathogenic Protein Aggregates Induce
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Therapeutic Strategies Targeting Misfolded Pathologic Protein Aggregate–Mediated Neuroinflammation
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Limitations of the Different Therapeutic Strategies
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Acknowledgments
Chapter 2: Synuclein misfolding as a therapeutic target
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Abstract
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Introduction
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The Conformational Landscape of α-Synuclein: the Native State
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The Conformational Landscape of α-Synuclein: Misfolded Variants
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Misfolding of α-Synuclein as a Therapeutic Target
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Conclusions
Chapter 3: Neuroinflammation as a therapeutic target in neurodegenerative diseases
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Abstract
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Introduction
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Glial Cells in CNS Development, Homeostasis, and Pathology
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Chronic Neuroinflammation as a Common Pathophysiological Mediator in Progressive Neurodegenerative Diseases
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Therapeutic Strategies Targeting Neuroinflammation in Progressive Neurodegenerative Diseases
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Future Perspectives
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Conclusions
Chapter 4A: Stem cells in neurodegeneration: mind the gap
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Abstract
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Introduction
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Part I: Stem Cells
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Part II: Stem Cells as Regenerative Therapy
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Part III: Stem Cells to Model Neurodegenerative Diseases
Chapter 4B: The potential of stem cells in tackling neurodegenerative diseases
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Abstract
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Endogenous Stem Cells as a Therapeutic Target
Chapter 5: Preclinical models of Alzheimer’s disease for identification and preclinical validation of therapeutic targets: from fine-tuning strategies for validated targets to new venues for therapy
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Abstract
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Introduction
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Conclusions
Chapter 6: Parkinson’s disease
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Abstract
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Introduction
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Current Treatment Approaches in Parkinson’s Disease
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Drugs That are Being Evaluated Clinically for Disease Modification in PD
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Novel Targets for Disease-Modifying Therapies in PD
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Conclusions
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Acknowledgments
Chapter 7: Lewy body dementia
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Abstract
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Lewy Body Dementia
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Management of LBD
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Concluding Remarks
Chapter 8: Frontotemporal dementia
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Abstract
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Overview of Frontotemporal Dementia
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Disease Management
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Novel Possibilities in Disease-Modifying Drug Development
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Discussion: Essentials for the Development of a Disease-Modifying Therapy
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Conclusions
Chapter 9: From huntingtin gene to Huntington’s disease-altering strategies
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Abstract
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Huntington’s Disease
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Huntingtin Gene and Transcripts
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Huntingtin Protein
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HD Pathogenic Mechanisms
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Molecular Strategies for HD
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ASO
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Genome Editing
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Conclusions and Perspectives
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Acknowledgments
Chapter 10: Amyotrophic lateral sclerosis: mechanisms and therapeutic strategies
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Abstract
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Introduction
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Excitotoxicity
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Hyperexcitability
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Pathogenic Role of Non-Neuronal Cells
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Shortage of Neurotrophic Factors
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Mitochondrial Dysfunction
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Axonal Defects
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Altered Proteostasis and Autophagy
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Altered RNA Metabolism and Stress Granule Formation
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Hexanucleotide Repeats in C9ORF72 and Disturbances in Nucleocytoplasmic Transport
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Conclusions
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Acknowledgments