Note: 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. , 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. , mHTT interactions with the translation machinery -- mHTT interactions with molecular chaperones -- Pathways implicated in mHTT clearance -- mHTT sequestration-beneficial or deleterious? -- A vicious cycle links proteostasis dysfunction and HD pathology -- Perspectives -- Chapter 10. Autophagy and Huntington's disease -- Introduction -- Autophagy, three pathways trafficking cytosolic cargo to the lysosome -- Autophagy: A therapeutic avenue for HD? -- Selective autophagy: No longer simply "bulk degradation" -- Dysfunctional autophagy in Huntington's disease -- Conclusion -- Chapter 11. SUMO modification in Huntington's disease: Unraveling complex mechanisms for therapeutic insights -- Introduction -- Unveiling the intricate machinery behind SUMOylation -- SUMO's journey in HD: Tracing SUMO's path in Huntington's disease research -- Guiding the way: E3 SUMO ligases and their role in regulating HTT protein dynamics -- Balancing act: How SUMO tips the scale of protein homeostasis -- SUMO at the crossroads of cellular stress: Navigating the relationship with stress granules -- Disruption of the nuclear pore and altered nucleocytoplasmic transport in HD: A role for SUMO? -- Synaptic SUMO: Bridging the gap between molecular modification and neuronal communication -- Small modifier, big role: How SUMO orchestrates DNA damage repair -- Summary and future directions: Implications for therapy -- Chapter 12. Selective vulnerability in Huntington's disease: From excitotoxicity, mitochondrial dysfunction, and transcription dysregulation to therapeutic opportunity -- Selective vulnerability in Huntington's disease -- Possible mechanisms underlying corticostriatal degeneration in HD -- Discovery of mitochondrial dysfunction in HD -- PGC-1α -- p53 and mitochondrial dysfunction in HD -- Heat Shock Transcription Factor 1 -- Peroxisome proliferator-activated receptors. , 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. , 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. , Micro-RNA: Its utility for viral-based delivery to brain in HD.

Note: Förderkennzeichen BMBF 01GR0445 [falsch] - 01GR0455 [richtig]. - Verbund-Nr. 01033926. - Engl. Berichtsbl. u.d.T.: SMP-bioinformatics: geneset analysis , Unterschiede zwischen dem gedruckten Dokument und der elektronischen Ressource können nicht ausgeschlossen werden , Auch als gedr. Ausg. vorhanden , Systemvoraussetzungen: Acrobat reader.