Huntington's disease : pathogenic mechanisms and implications for therapeutics /

Huntington's disease (HD) is one of the most common dominantly inherited neurodegenerative disorders, characterized by a clinical trial of movement disorder, cognitive deficits, and psychiatric symptoms.

Bibliographic Details
Uniform Title:Huntington's disease (Yang)
Corporate Author: ScienceDirect (Online service)
Other Authors: Yang, X. William (Editor), Thompson, Leslie M. (Professor) (Editor), Heiman, Myriam (Editor)
Format: eBook
Language:English
Published: London : Academic Press, 2024.
Subjects:
Online Access:Connect to the full text of this electronic book

MARC

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245 0 0 |a Huntington's disease :  |b pathogenic mechanisms and implications for therapeutics /  |c edited by X. William Yang, Leslie M. Thompson, Myriam Heiman. 
264 1 |a London :  |b Academic Press,  |c 2024. 
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505 0 |a Intro -- Title page -- Table of Contents -- Copyright -- Dedication -- Contributors -- Preface -- Chapter 1. Huntington's disease: Clinical features, genetic diagnosis, and brain imaging -- Introduction -- Clinical course -- Juvenile Huntington's disease -- Genetic diagnosis and genetic counseling -- Imaging -- Conclusion: Clinical aspects relevant for the development of disease-modifying therapies in Huntington's disease -- List of abbreviations -- Chapter 2. Revolutionizing clinical research and communication in Huntington's disease: The Huntington's disease integrated staging system (HD-ISS) -- Introduction -- Disease classification, measurement, and staging -- The development of the HD-ISS -- Applying the HD-ISS in research: New possibilities -- Applying the HD-ISS in research: Practical questions -- Applying the HD-ISS in research: Implications for people with Huntington's disease -- Conclusion -- Chapter 3. Huntington's disease genetics: Implications for pathogenesis -- Description of inheritance -- Chromosomal mapping of the HD genetic defect and its consequences -- The HD genetic defect -- The expanded HTT CAG repeat confers a gain of function -- HD genotype-phenotype correlation -- Modifiers of HD onset from human genetics -- A model for HD pathogenesis from human genetics -- Underpinnings of the modifier effects -- Modifiers of other disease landmarks -- HD diagnostics -- What is the ultimate cause of neuronal loss? -- Potential for developing an HD treatment from genetic knowledge -- Conclusion -- Chapter 4. The instability of the Huntington's disease CAG repeat mutation -- Introduction: The critical role of CAG repeat length -- Intergenerational repeat instability -- Somatic repeat instability -- Insights into CAG repeat instability from mouse models -- Insights from human genetics -- Conclusions and perspective. 
505 8 |a Chapter 5. Mechanisms of somatic CAG-repeat expansions in Huntington's disease -- Introduction -- Current understanding of somatic repeat instability -- Slip-out formation -- Requirement of transcription and transcription-coupled repair for somatic repeat instability -- Melting unusual structures at the repeat and modulating torsional tension -- Many nucleases can act on slipped-DNA structures which may impact repeat instability -- Gap-filling and ligation of the DNA backbone -- What is still unclear? -- Conclusion -- Chapter 6. RNA-mediated pathogenic mechanisms in Huntington's disease -- Expression of the huntingtin gene -- Regulation of huntingtin transcription -- Alternative processing of huntingtin pre-mRNA -- Nuclear RNA "clusters" and RNA "foci" in HD mouse models and HD patient samples -- Global aberrant RNA processing in HD -- RNA-based mechanism of pathogenesis -- Implications for therapy -- Chapter 7. Huntingtin protein-protein interactions: From biology to therapeutic targets -- Introduction -- Two-hybrid HTT protein interaction mapping efforts -- Cataloging of HTT interacting partners using (immuno)affinity-based purification approaches -- Compilation and computational analysis of HTT PPIs from large- and small-scale PPI mapping studies -- Outlook -- Chapter 8. Repeat-associated non-AUG (RAN) translation and Huntington's disease: Pathology, mechanistic and therapeutic perspectives -- Introduction to RAN translation -- RAN proteins in Huntington's disease -- RAN and polyGln proteins accumulate in distinct and vulnerable brain regions -- Animal models of HD and RAN translation -- RAN protein toxicity -- Mechanistic focused therapeutics -- Conclusions -- Chapter 9. Proteostasis function and dysfunction in Huntington's disease -- Introduction -- Impact of mHTT protein on HD pathology and protein aggregation propensity. 
505 8 |a Therapeutic opportunities -- Conclusion and future directions -- Chapter 13. Pathophysiology of synapses and circuits in Huntington disease -- Clinical and genetic features of HD -- Cortical-basal ganglia-thalamic-cortical loops regulate movement and are modulated by dopamine -- Neuropathology -- Measurable subclinical changes precede definitive motor diagnosis -- Animal models of HD facilitate investigating brain changes before overt clinical diagnosis -- Striatal microcircuit synapses -- Synaptic alterations in basal ganglia nuclei downstream of striatal SPN -- Neuronal excitability -- Input-specific plasticity: Long-term potentiation and depression -- Homeostatic plasticity -- Altered corticostriatal and thalamostriatal connectivity in HD -- Cortex motor and sensory function -- Cortex reward pathways -- Targeting synaptic and circuit changes to advance therapeutics in Huntington disease -- Chapter 14. The role of glial pathology in Huntington's disease -- The role of glial progenitor cells in HD pathogenesis -- Astrocytic dysfunction in HD -- The effects of HD pathology on oligodendrocytes and myelin -- Synopsis -- Chapter 15. Systems biology study of Huntington's disease -- Introduction -- Transcriptomic profiling of HD mice -- Insights from transcriptomic studies of HD mouse models -- Mechanisms implicated in striatal transcriptinopathy in HD -- Epigenomic dysregulation in HD mice -- Application of systems biology to study HD perturbations -- Database of HD experimental data -- Conclusions and perspectives -- Chapter 16. Unbiased genome-wide approaches to identify vulnerability factors in Huntington's disease -- Yeast model screening studies -- Invertebrate model screening studies -- Mammalian cell screening studies -- Mammalian in vivo screening -- Future directions. 
505 8 |a Chapter 17. Striatal neuronal models of Huntington's disease via direct conversion: Modeling age-dependent disease phenotypes -- MicroRNA-mediated conversion of human fibroblasts to neurons -- Age maintenance in directly reprogrammed neurons -- Recapitulation of adult-onset neuropathology of Huntington's disease using miRNAs-mediated reprogrammed neurons -- Modeling disease-stage progression of Huntington's disease -- Conclusion -- Chapter 18. Genetic mouse models to explore Huntington's disease mechanisms and therapeutic strategies -- Transgenic mHTT N-terminal fragment mouse models of HD -- Full-length mHTT knock-in mouse models -- Full-length human HTT transgenic models -- Conclusions and perspectives -- Chapter 19. Huntington's disease: From large animal models to HD gene therapy -- Introduction to Huntington's disease neuropathology -- Treatment of large animal models of HD -- Conclusions -- Chapter 20. Deep learning and deep phenotyping of HD iPSCs: Applications to study biology and test therapeutics -- Background: Complexity in biology -- A brief introduction to AI -- Applications of DL to biology -- Impact -- Chapter 21. The promise of an underappreciated therapeutic target: Sleep and circadian rhythm dysfunction in Huntington's disease -- Sleep disturbance in Huntington's disease: The evidence -- Sleep disturbance in Huntington's disease: Preclinical models -- Which comes first, HD or sleep dysfunction, and does it matter? -- Circadian-based interventions in preclinical models -- Pharmacological interventions -- Conclusions -- Chapter 22. Huntingtin lowering therapeutics -- DNA oligonucleotides -- Oligonucleotides that use RNA interference -- siRNA oligonucleotides as therapeutic agents in HD -- Gene editing to lower or correct mutant huntingtin mRNA or protein -- AAV gene delivery for Huntington's disease: Background. 
504 |a Includes bibliographical references and index. 
588 |a Description based on print version record. 
520 |a Huntington's disease (HD) is one of the most common dominantly inherited neurodegenerative disorders, characterized by a clinical trial of movement disorder, cognitive deficits, and psychiatric symptoms. 
650 0 |a Huntington's disease. 
655 7 |a Electronic books.  |2 local 
700 1 |a Yang, X. William,  |e editor. 
700 1 |a Thompson, Leslie M.  |c (Professor),  |e editor. 
700 1 |a Heiman, Myriam,  |e editor. 
710 2 |a ScienceDirect (Online service) 
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