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Fragile X syndrome : from genetics to targeted treatment /
| Clasificación: | Libro Electrónico |
|---|---|
| Otros Autores: | , |
| Formato: | Electrónico eBook |
| Idioma: | Inglés |
| Publicado: |
London :
Academic Press,
[2017]
�2017 |
| Temas: | |
| Acceso en línea: | Texto completo |
MARC
| LEADER | 00000cam a2200000Ia 4500 | ||
|---|---|---|---|
| 001 | SCIDIR_ocn988378489 | ||
| 003 | OCoLC | ||
| 005 | 20231120112236.0 | ||
| 006 | m o d | ||
| 007 | cr |n||||||||| | ||
| 008 | 170530s2017 enk ob 001 0 eng d | ||
| 040 | |a YDX |b eng |e pn |c YDX |d N$T |d IDEBK |d EBLCP |d N$T |d OPELS |d OCLCF |d MERER |d OCLCQ |d OTZ |d COD |d OCLCQ |d D6H |d DKU |d UAB |d OCLCQ |d U3W |d TSC |d AU@ |d OCLCQ |d S2H |d OCLCO |d OCLCQ |d SFB |d OCLCQ |d OCLCO | ||
| 019 | |a 988556015 | ||
| 020 | |a 9780128045077 |q (electronic bk.) | ||
| 020 | |a 0128045078 |q (electronic bk.) | ||
| 020 | |z 9780128044612 | ||
| 020 | |z 0128044616 | ||
| 035 | |a (OCoLC)988378489 |z (OCoLC)988556015 | ||
| 050 | 4 | |a RJ506.F73 | |
| 072 | 7 | |a MED |x 069000 |2 bisacsh | |
| 072 | 7 | |a HEA |x 046000 |2 bisacsh | |
| 082 | 0 | 4 | |a 616.85/884 |2 23 |
| 245 | 0 | 0 | |a Fragile X syndrome : |b from genetics to targeted treatment / |c edited by Rob Willemsen, R. Frank Kooy. |
| 260 | |a London : |b Academic Press, |c [2017] | ||
| 264 | 4 | |c �2017 | |
| 300 | |a 1 online resource | ||
| 336 | |a text |b txt |2 rdacontent | ||
| 337 | |a computer |b c |2 rdamedia | ||
| 338 | |a online resource |b cr |2 rdacarrier | ||
| 504 | |a Includes bibliographical references and index. | ||
| 588 | 0 | |a Online resource, title from PDF title page (EBSCO, viewed June 7, 2017). | |
| 505 | 0 | |a Section I -- Clinics, Diagnosis, Epidemiology, Molecular Mechanisms, and Models -- Chapter 1 -- The Clinical Phenotype of the Fragile X Syndrome and Related Disorders -- Introduction -- The fragile X syndrome -- Background -- Physical Manifestations -- Epilepsy -- Cognition -- The Behavioral Phenotype -- Treatment -- Fragile X tremor ataxia syndrome -- The fragile X premature ovarian insufficiency -- Acknowledgments -- References -- Chapter 2 -- Fragile X Syndrome Genetics -- Setting the stage -- Genetic Oddities -- Positional cloning of FRAXA and FMR1 -- FMR1 Structure and Function -- FMRP and mRNA metabolism -- Resolving the Sherman paradox -- Premutation disorders -- Origins of FXS -- Conclusions and perspectives -- References -- Chapter 3 -- Molecular Diagnostics and Genetic Counseling in Fragile X Syndrome and FMR1-Associated Disorders -- Fragile X syndrome -- The diagnosis of fragile X syndrome -- Genetic counseling in FMR1-associated disorders -- Normal Range -- Intermediate Alleles or Gray Zone -- Premutation Alleles -- Full Mutation Alleles -- References -- Chapter 4 -- Epidemiology of Fragile X Syndrome -- Introduction -- Prevalence of FXS -- Prevalence of FXS among subpopulations -- Factors related to variation in clinical presentation affect the ability to estimate prevalence -- Deletions and point mutations leading to FXS -- Conclusions -- References -- Chapter 5 -- Mechanisms of Repeat Instability in Fragile X Syndrome -- Introduction -- Factors That Affect Expansion Risk -- Parallels to Other Related Disorders -- Model Systems to Study Repeat Instability -- Potential mechanisms for repeat expansion -- Instability May be Initiated by Secondary Structures Formed by the Repeats. | |
| 505 | 8 | |a The Effect of These Secondary Structures May be Mediated via Mismatch Repair Proteins -- S-Phase Dependent Models for Repeat Expansion -- S-Phase Independent Expansion Models -- Potential mechanisms for contraction and error-free repair -- Do chromosome fragility and repeat expansion share a common mechanism? -- Concluding remarks and future directions -- Acknowledgments -- Glossary of terms -- References -- Further Reading -- Chapter 6 -- Modeling Fragile X Syndrome Using Human Pluripotent Stem Cells -- Human-based models for FXS -- Modeling FXS in human pluripotent stem cells -- Human ESCs as a developmental model for FXS -- iPSCs in modeling fragile X syndrome -- Neural differentiation of FXS-PSCs -- PSC modeling of CGG repeat instability -- The use of FXS-PSCs for targeted drug discovery -- Conclusions -- References -- Chapter 7 -- Animal Models of Fragile X Syndrome -- Introduction -- Rodent models of fragile X syndrome -- Mouse models of fragile X syndrome -- The phenotypic spectrum of the knockout mouse -- Neuroanatomical Phenotype in Fmr1 Knockout Mouse -- Long-Term Potentiation and Long-Term Depression -- Behavioral Phenotype in Fmr1 Knockout Mouse -- Seizures and Hypersensitivity -- Cognitive Functioning -- Attention and Hyperactivity -- Social and Emotional Functioning -- Anxiety -- Rat models of fragile X syndrome -- Zebra fish models of fragile X syndrome -- Drosophila Models of Fragile X Syndrome -- FMRP Protein is Well-Conserved Between Drosophila and Mammals -- FXS Fly Model Displays the Defects in Behavior, Synaptogenesis and Spermatogenesis -- Behavioral Defects -- Synaptogenesis Defects -- Spermatogenesis Abnormality -- Utilities of Fly Model Toward Understanding the Molecular Basis of FXS -- Concluding remarks -- References -- Section II -- Pathways involved -- Chapter 8 -- RNA and Protein Targets of FMRP -- Introduction. | |
| 505 | 8 | |a Approaches to defining the RNAs/proteins associated with FMRP -- Molecular Approaches -- Cell Biology and Proteomic Approaches -- Computational Approaches -- FMRP-binding determinants -- Structural RNA Motifs Targeted by FMRP -- Sequence Motifs Targeted by FMRP -- Non-RNA FMRP Interactions -- Conclusions -- References -- Chapter 9 -- The mGluR Theory of Fragile X: From Mice to Men -- Introduction -- FMRP negatively regulates translation -- Animal models of FXS -- Dysregulation of synaptic protein synthesis in the Fmr1 KO mouse -- The mGluR theory of FXS -- Correcting FXS: targeting mGlu5 -- Correcting FXS: targeting translation control -- Targeting ERK -- Targeting mTOR -- Targeting p70 S6K -- Targeting GSK3[alpha]/[beta] -- Correcting FXS: other targets -- From mice to men: clinical trials for FXS -- Failure in the clinic and what we can learn -- New directions -- Beta Arrestins: a Scaffold for Ras-ERK and Modulator of Signaling -- GSK3[alpha] and GSK[beta] -- Novel Targets From the FXS Translatome -- Concluding remarks -- References -- Further Reading -- Chapter 10 -- The GABAergic System Contributions to the Fragile X Syndrome Phenotype -- Introduction -- Inhibitory interneuron dysfunction in FXS -- Synaptic components at GABAergic synapses are dysregulated in FXS -- Targeting deficiencies of the GABAergic system in FXS as viable treatment options -- Preventing depolarizing GABAergic potentials in developing circuits -- Conclusions -- Acknowledgment -- References -- Further reading -- Chapter 11 -- Intracellular Signaling Networks in Fragile X Syndrome: Approaches to Drug Discovery and Therapeutics -- Introduction -- Dysregulated PI3K signaling in FXS -- PI3K Downstream Signaling is Defective in FXS Mouse Models -- FMRP Regulates PI3K Activity by Controlling mRNA Translation and Protein Expression of PI3K Catalytic and Regulatory Subunits. | |
| 505 | 8 | |a Enhanced PI3K Activity in Peripheral Blood Cells and Tissue From Individuals with FXS -- Dysregulated ERK1/2 signaling in FXS -- Impaired Stimulus-Induced ERK1/2 Activation: A First Potential Biomarker in FXS -- Does Defective ERK1/2 Signaling Contribute to the FXS Phenotype? -- Aberrant ERK1/2 Activation as Potential Biomarker in Clinical Trials -- Targeting the signaling hub Ras to correct altered signaling in FXS -- TSC-mTORC1-S6K1-4EBP nexus: a major mRNA translation control node in FXS -- TSC 1-2 complex is a vital, but understudied signaling node for FXS -- mTOR is a well-studied candidate in FXS, but may not be suited for direct therapeutic intervention -- S6K1: a signal integrator and translational regulator with therapeutic potential in FXS -- S6K1 Shows Subtly Different Effects in Genetic Deletion and Pharmacological Inhibition Studies -- Modulation eIF4E via Mnk1 offers an alternative to managing FXS phenotypes -- Challenges and Future Outlook -- Acknowledgments -- References -- Further Reading -- Chapter 12 -- The Endocannabinoid System in Fragile X Syndrome -- Introduction -- The Endocannabinoid System -- Molecular alterations in FXS -- Inhibitory neurotransmission -- Hippocampal DSI -- Modulation of mGluR5-Coupled Function by Homer -- Endocannabinoid Modulation of Striatal Neurotransmission -- Excitatory neurotransmission -- Endocannabinoid-Mediated Long-Term Depression (eCB-LTD) -- Findings in Other Nonsyndromic Models -- Neuroligin 3 -- Endocannabinoid system interventions -- Conclusions/Perspectives -- Acknowledgments -- References -- Chapter 13 -- Glycogen Synthase Kinase-3: Abnormalities and Therapeutic Potential in Fragile X Syndrome -- Introduction -- Fragile X syndrome: etiology and animal models -- Glycogen synthase kinase-3 -- Morphological and biochemical effects of GSK3 inhibition in Fmr1 knockout mice. | |
| 505 | 8 | |a Behavioral abnormalities in Fmr1 knockout mice improved by GSK3 inhibitor treatments -- Cognitive impairments in Fmr1 knockout mice rescued by administration of GSK3 inhibitors -- Electrophysiological abnormalities in Fmr1 knockout mice improved by GSK3 inhibitors -- Clinical trials -- Summary -- Acknowledgments -- References -- Chapter 14 -- Defects in Rho GTPase Signaling to the Spine Actin Cytoskeleton in FMR1 Knockout Mice -- Introduction -- Fragile X and Disturbances in Spine Morphology -- Fmr1 KO Mice Exhibit Hippocampal Synaptic Plasticity Defects -- Changes in the spine actin cytoskeleton support synaptic plasticity -- Fmr1 KO defects in Rho GPTase signaling pathwayproteins -- Cofilin (ADF/Cofilin Family) -- PAK (p21 Activated Kinase) -- Cortactin (Cortical Actin Binding Protein) -- ERK1/2 (Extracellular Signal-Regulated Kinase) -- Conclusions and future directions -- Acknowledgments -- References -- Chapter 15 -- Matrix Metalloproteinases in Fragile X Syndrome -- Introduction -- FMR1-deficiency and dendritic spine morphology -- Extracellular matrix -- Metalloproteinases -- MMP-9 in FXS -- Conclusions -- Abbreviations -- References -- Further Readings -- Chapter 16 -- Ion Channel Dysfunction and FXS -- Introduction -- Voltage-dependent potassium channels -- FMRP Regulates Kv3.1 Voltage-Dependent Channels That are Required for High Frequency Firing -- Kv1 Family Channels -- Kv4.2 Channels -- BKCa Channels -- FMRP Directly Binds Slack KNa1.1 Channels -- Nonselective cation channels -- HCN Channels -- Calcium channels -- L-Type Ca2+ Channels -- N-Type Ca2+ Channels -- Conclusions -- References -- Chapter 17 -- Reactivation of the FMR1 Gene -- Introduction -- Epigenetic status of premutated alleles -- Epigenetic silencing of FMR1 full mutation -- Rare individuals with unmethylated full mutation -- Treatment options for FXS. | |
| 650 | 0 | |a Fragile X syndrome |x Treatment. | |
| 650 | 0 | |a Fragile X syndrome |x Genetic aspects. | |
| 650 | 6 | |a Syndrome de l'X fragile |0 (CaQQLa)201-0143348 |x Traitement. |0 (CaQQLa)201-0377521 | |
| 650 | 6 | |a Syndrome de l'X fragile |x Aspect g�en�etique. |0 (CaQQLa)201-0361170 | |
| 650 | 7 | |a MEDICAL |x Pediatrics. |2 bisacsh | |
| 650 | 7 | |a HEALTH & FITNESS |x Children's Health. |2 bisacsh | |
| 650 | 7 | |a Fragile X syndrome |2 fast |0 (OCoLC)fst00933571 | |
| 700 | 1 | |a Willemsen, Rob, |e editor. | |
| 700 | 1 | |a Kooy, R. Frank, |e editor. | |
| 776 | 0 | 8 | |i Print version: |z 9780128044612 |z 0128044616 |w (OCoLC)960845349 |
| 856 | 4 | 0 | |u https://sciencedirect.uam.elogim.com/science/book/9780128044612 |z Texto completo |