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035			_a(OCoLC)1451830467 _z(OCoLC)1451832662
040			_aDXU _beng _erda _epn _cDXU _dOCLCO _dOCLCL _dOCLCQ
050		4	_aRC406.A24 _b.S643 2021
082	0	4	_a616.83 _223
245	0	0	_aSpectrums of amyotrophic lateral sclerosis : _bheterogeneity, pathogenesis and therapeutic directions / _cedited by Christopher A. Shaw and Jessica R. Morrice.
246	3		_aSpectrums of Amyotrophic Lateral Sclerosis
260			_bJohn Wiley & Sons, Ltd.
264		1	_aHoboken, NJ : _bJohn Wiley & Sons, Inc., _c[2021]
264		4	_c�2021
300			_a1 online resource (237 pages)
336			_atext _btxt _2rdacontent
337			_acomputer _bc _2rdamedia
338			_aonline resource _bcr _2rdacarrier
505	0		_aCover -- Title Page -- Copyright Page -- Contents -- Contributors -- Foreword -- Preface -- Acknowledgments -- Chapter 1 Clinical Heterogeneity of ALS -- Implications for Models and Therapeutic Development -- Introduction -- Clinical Heterogeneity of ALS -- Familial and Sporadic ALS -- Age of Onset -- Survival -- Classic ALS, LMN Form, and UMN Form -- Site of Onset -- Diagnosis of ALS -- ALS and Its Relationship with Frontotemporal Dementia and Myopathies -- Pleiotropy of ALS Genes -- Genetic Models to Study ALS -- In Vivo Models -- In Vitro Models -- Conclusion -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 2 Genetic Basis of ALS -- Introduction -- Genes Causing ALS -- Superoxide Dismutase 1 (SOD1) -- TAR DNA-Binding Protein 43 (TDP-43) -- Fused in Sarcoma (FUS) -- Chromosome 9 Open Reading Frame 72 (C9orf72) -- Recently Discovered Genes -- Annexin A11 (ANXA11) -- Glycosyltransferase 8 Domain Containing 1 (GLT8D1) -- Stathmin-2 (STMN2) -- Aspects of ALS Heritability -- Sporadic vs. Familial -- Penetrance and the Oligogenic Hypothesis -- Multistep Model -- Noncoding Variation -- Regulatory and Intronic Variants -- Epigenetics -- Conclusions -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 3 Susceptibility Genes and Epigenetics in Sporadic ALS -- Introduction -- Environmental Associations in sALS -- Genetic Basis of sALS -- Identification of sALS Susceptibility Genes -- Candidate sALS Susceptibility Genes -- UNC13A -- DPP6 -- C21orf2 -- Epigenetic Mechanisms in sALS -- Methylation in sALS -- miRNAs in sALS -- Post-Translational Histone Modification in sALS -- Epigenetic Analysis in Monozygotic sALS Twins -- Modifications to the Epigenome by Environmental Factors -- In Utero Environmental Exposures -- Environmental in Utero Epigenomic Alterations.
505	8		_aPost Utero Exposures -- Conclusion -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 4 The Lessons of ALS-PDC -- Environmental Factors in ALS Etiology -- Introduction -- Koch's Postulates in the Search of Etiological ALS Factors -- Neurological Disease Clusters -- The Natural History of ALS-PDC -- Investigating Etiological Factors -- Identified Cycad toxin/Toxicants -- Aluminum and Ionic Etiologies for ALS-PDC -- Other Molecules That Might Have Been Involved in ALS-PDC -- A Putative Viral Etiology for ALS-PDC on Guam and ALS in General -- The Continuing Importance of ALS-PDC -- Summary and Conclusions -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- Note -- References -- Chapter 5 The Microbiome of ALS -- : Does It Start from the Gut? -- Introduction -- Recent Studies -- Animal and in vitro Studies -- Clinical Studies -- How Could the Microbiome Contribute to ALS? -- Gut Barrier and Membrane Permeability -- Inflammation and Immune Response -- Neurotoxins -- Energy Metabolism -- Microbiome Modulation as a Potential Therapeutic Avenue -- Conclusion -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 6 Protein Aggregation in Amyotrophic Lateral Sclerosis -- Introduction -- Pathological Protein Inclusions Associated with ALS -- Protein Homeostasis and Misfolded Protein Partitioning in ALS -- Consequences of Protein Aggregation in ALS -- The Primary Aggregating Proteins in ALS -- Superoxide Dismutase-1 (SOD1) -- Transactivation Response DNA Binding Protein 43 (TDP-43) -- Fused in Sarcoma (FUS) -- Prion-like Propagation of Protein Aggregation in ALS -- Conclusion -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 7 Evidence for a Growing Involvement of Glia in Amyotrophic Lateral Sclerosis.
505	8		_aIntroduction -- Non-neuronal Cells Play Important Roles in Neurodegeneration Including in ALS -- Glial Cells and Their Established Functions -- Neurodegeneration and the Role of Glial Cells -- Glia in ALS -- Glial Dysfunction Is a Common Hallmark of ALS Patients -- Glial Activation in ALS Models -- Major Pathological Forms of ALS -- Microglia-Related ALS Pathology -- Microglia in SOD1-ALS Pathology -- Microglia in TDP-43-ALS Pathology -- Microglia in FUS-ALS Pathology -- Astrocyte-Related ALS Pathology -- Oligodendrocyte-Related ALS Pathology and Glial Inclusion Formation -- Glial Inclusion Formation in ALS -- Oligodendrocytes -- Astrocytes -- The Role of Glial Cells in SOD1 Pathology Might Be Different from Other Forms of ALS -- Conclusion -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 8 Animal Models of ALS -- Current and Future Perspectives -- Introduction -- The Clinical Manifestations of ALS -- Limb Onset -- Bulbar Onset -- Respiratory Onset -- Current and Experimental Pharmacological Interventions -- Riluzole -- Edaravone -- Future Directions for Pharmacological Interventions -- Causative Factors in the Development of ALS -- Genetic Factors -- Environmental and Epigenetic Factors -- Gut and Microbial Factors -- Animal Models of ALS -- One-hit Models of ALS -- Multi-hit Models of ALS -- Future Model Development -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 9 Clinical Trials in ALS -- Current Challenges and Strategies for Future Directions -- Introduction -- Challenges in ALS Clinical Trials -- Disease Heterogeneity -- Lack of Established Biomarkers -- Limitations of Conventional Outcome Measures -- ALSFRS-R -- FVC/SVC -- HHD -- Survival vs. Function -- Phase II Trial "Paradox" -- Patient Recruitment and Retention.
505	8		_aAssumptions for Lead-In Phases -- Navigating Regulatory Nuances -- Future Directions -- Advances in Disease Understanding and Assessment -- Disease Heterogeneity -- Emerging Biomarkers -- Novel Outcome Measures -- New Approaches to Trial Design -- Cautious Phase II Design -- Adaptive Trial Design -- Platform Trials -- Bayesian Statistics -- Education -- People Make or Break a Trial -- Conclusion -- Acknowledgments -- Conflict of Interest -- Copyright and Permission Statement -- References -- Chapter 10 Future Priorities and Directions in ALS Research and Treatment -- Introduction -- Etiological Heterogeneity of ALS -- ALS Risk Factors -- Cellular Dysfunction in ALS -- ALS as a "Treatable" Disease -- The Importance of Effective Biomarkers -- Future Therapeutic Avenues for a Heterogeneous Disease -- Ongoing Clinical Trials Using CuATSM -- Conclusions and the Road Forward in ALS Research and Treatment -- Conflict of Interest -- Copyright and Permission Statement -- References -- Index -- EULA.
520			_a"Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder affecting both upper and lower motor neurons. Based on age at onset, site of onset, disease duration, and relative predominance of upper or lower motor neuron signs, clinical manifestations of ALS are very heterogeneous, and different clinical subtypes may be delineated. Although ALS has long been considered a paradigm of pure motor neuron disorder, it has recently been linked to other neurological diseases. Clinical, genetic, and/or neuropathological overlap exists with frontotemporal dementia, distal myopathies, psychiatric disorders, and extrapyramidal syndromes. This clinical heterogeneity can depend on the pleiotropy of ALS-associated genes and by the oligogenic model of disease mechanism. A number of animal models have been created, each of them recapitulating some clinical and neuropathological features of patients. More recently, induced pluripotent stem cells have been used, directly derived from affected patients with different genetic mutations. The combination of animal and cellular models represents an advanced tool that can help to functionally characterize the pathogenetic mechanisms underlying the disease and specifically find efficient and personalized drugs to treat ALS patients"-- _cProvided by publisher.
588			_aDescription based on print version record.
650		0	_aAmyotrophic lateral sclerosis _xGenetic aspects.
650		0	_aAmyotrophic lateral sclerosis _xChemotherapy.
650		6	_aScl�erose lat�erale amyotrophique _xAspect g�en�etique.
650		6	_aScl�erose lat�erale amyotrophique _xChimioth�erapie.
700	1		_aShaw, Christopher A., _eeditor.
700	1		_aMorrice, Jessica R., _eeditor.
776	1		_z1119745497
942			_2lcc _cBK _n0
948			_h
999			_c36858 _d36858