Spectrums of Amyotrophic Lateral Sclerosis - Heterogeneity, Pathogenesis and Therapeutic Directions

SPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS
 
Discover state-of-the-art research findings on ALS from leading authors and editors in the field
 
In Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies.
 
In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed.
 
Readers will also benefit from the inclusion of:
* A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial design
* Explorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALS
* Discussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cells
* Examinations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategies
 
Perfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.

List of contents

Contributors xiii
 
Preface xvii
 
Acknowledgments xix
 
Foreword xxi
 
CHAPTER 1 Clinical Heterogeneity of ALS - Implications for Models and Therapeutic Development 1
 
Serena Lattante and Mario Sabatelli
 
Introduction 1
 
Clinical Heterogeneity of ALS 2
 
Familial and Sporadic ALS 2
 
Age of Onset 3
 
Survival 3
 
Classic ALS, LMN Form, and UMN Form 4
 
Site of Onset 4
 
Diagnosis of ALS 5
 
ALS and Its Relationship with Frontotemporal
 
Dementia and Myopathies 5
 
Pleiotropy of ALS Genes 6
 
Genetic Models to Study ALS 8
 
In Vivo Models 8
 
In Vitro Models 9
 
Conclusion 10
 
Conflict of Interest 11
 
Copyright and Permission Statement 11
 
References 11
 
CHAPTER 2 Genetic Basis of ALS 17
 
Jay P. Ross, Patrick A. Dion, and Guy A. Rouleau
 
Introduction 17
 
Genes Causing ALS 18
 
Superoxide Dismutase 1 (SOD1) 18
 
TAR DNA-Binding Protein 43 (TDP-43) 19
 
Fused in Sarcoma (FUS) 19
 
Chromosome 9 Open Reading Frame 72 (C9orf72) 20
 
Recently Discovered Genes 21
 
Annexin A11 (ANXA11) 21
 
Glycosyltransferase 8 Domain Containing 1 (GLT8D1) 23
 
Stathmin-2 (STMN2) 23
 
Aspects of ALS Heritability 24
 
Sporadic vs. Familial 24
 
Penetrance and the Oligogenic Hypothesis 24
 
Multistep Model 25
 
Noncoding Variation 25
 
Regulatory and Intronic Variants 25
 
Epigenetics 26
 
Conclusions 27
 
Acknowledgments 27
 
Conflict of Interest 27
 
Copyright and Permission Statement 28
 
References 28
 
CHAPTER 3 Susceptibility Genes and Epigenetics in Sporadic ALS 35
 
Jessica R. Morrice, Christopher A. Shaw,
 
and Cheryl Y. Gregory-Evans
 
Introduction 35
 
Environmental Associations in sALS 36
 
Genetic Basis of sALS 38
 
Identification of sALS Susceptibility Genes 39
 
Candidate sALS Susceptibility Genes 40
 
Unc13a 40
 
Dpp6 40
 
C21orf2 41
 
Epigenetic Mechanisms in sALS 41
 
Methylation in sALS 41
 
miRNAs in sALS 42
 
Post-Translational Histone Modification in sALS 43
 
Epigenetic Analysis in Monozygotic sALS Twins 44
 
Modifications to the Epigenome by Environmental Factors 44
 
In Utero Environmental Exposures 45
 
Environmental in Utero Epigenomic Alterations 45
 
Post Utero Exposures 45
 
Conclusion 46
 
Conflict of Interest 46
 
Copyright and Permission Statement 47
 
References 47
 
CHAPTER 4 The Lessons of ALS-PDC - Environmental Factors
 
in ALS Etiology 57
 
Christopher A. Shaw and Thomas E. Marler
 
Introduction 57
 
Koch's Postulates in the Search of Etiological ALS Factors 58
 
Neurological Disease Clusters 59
 
The Natural History of ALS-PDC 60
 
Investigating Etiological Factors 62
 
Identified Cycad Toxicants 67
 
Aluminum and Ionic Etiologies for ALS-PDC 69
 
Other Molecules That Might Have Been Involved in ALS-PDC 70
 
A Putative Viral Etiology for ALS-PDC on Guam
 
and ALS in General 70
 
The Continuing Importance of ALS-PDC 71
 
Summary and Conclusions 73
 
Acknowledgments 74
 
Conflict of Interest 74
 
Copyright and Permission Statement 74
 
References 75
 
CHAPTER 5 The Microbiome of ALS - Does It Start from the Gut? 81
&nbs

Summary

SPECTRUMS OF AMYOTROPHIC LATERAL SCLEROSIS

Discover state-of-the-art research findings on ALS from leading authors and editors in the field

In Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions, distinguished researchers and editors Dr. Christopher A. Shaw and Jessica R. Morrice deliver a practical and powerful perspective on Amyotrophic Lateral Sclerosis (ALS) as a heterogeneous spectrum of disorders. This increasingly accepted point-of-view allows researchers and medical professionals to develop better targeted interventions and more precise therapies.

In the book, readers will find chapters on a wide variety of critical issues facing ALS researchers and healthcare practitioners treating ALS sufferers, including animal models of ALS, neuronal support cells known to have a pivotal role in ALS, and current challenges in ALS clinical trials, among others. The authors describe pathologic features common to all cases of ALS and why animal models, though crucial, should be interpreted with caution. Finally, multiple genetic and environmental etiologies of the disease are discussed.

Readers will also benefit from the inclusion of:
* A thorough introduction to ALS as a spectrum disease and the implications for models, therapeutic development and clinical trial design
* Explorations of the genetic basis of ALS, prospective sALS etiologies, and the involvement of microbiome in ALS
* Discussions of ALS-PDC and environmental risk factors, protein aggregation in ALS, defects in RNA metabolism in ALS, and the non-cell autonomous nature of ALS and the involvement of glial cells
* Examinations of animal models of ALS and perspectives on previously failed ALS therapeutics and current therapeutic strategies

Perfect for clinical neurologists, healthcare providers and caretakers, clinicians, and researchers studying motor neuron disease, Spectrums of Amyotrophic Lateral Sclerosis: Heterogeneity, Pathogenesis & Therapeutic Directions is also an indispensable resource for the neurodegenerative research community, neurology residents, and graduate-level neuroscience students.

Product details

• Authors: Jessia R Morrice, Jessia R. Morrice, Jessica R. Morrice, CA Shaw, Christopher Shaw, Christopher A Shaw, Christopher A. Shaw, Christopher A. Morrice Shaw
• Assisted by: Christophe A Shaw (Editor), Christopher A Shaw (Editor), Jessica R. Morrice (Editor), R Morrice (Editor), R Morrice (Editor), Christopher A. Shaw (Editor), Shaw Christopher A. (Editor)
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 25.03.2021
• EAN: 9781119745495
• ISBN: 978-1-119-74549-5
• No. of pages: 240
• Subjects: Natural sciences, medicine, IT, technology > Biology; Neurologie, Medizin, Neurowissenschaften, Life Sciences, Neurology, Neuroscience, Biowissenschaften, Medical Science