Neural dynamics of neurological disease / Christopher A. Shaw. -- Hoboken, New Jersey : John Wiley & Sons, Inc., c2017. – (64.1/S534n)

Contents

Preface  xv

Acknowledgments  xxi

Part I   The Dynamics of Neurological Disease  1

1  The Dynamics of Neurological Disease: Current Views and Key Issues  3

1.1     Introduction  4

1.2     The Complexity of Human Neurological Diseases  4

1.3     The Nervous System as an Archetypical Complex System  9

1.4     CNS Signaling Failures: Implications for Neurological Disease  14

1.5     History and Key Characteristics of the Age-Dependent Neurological Diseases  14

1.6     The Fractal Nature of Complexity in the CNS  16

        Endnotes  17

2  Clinical and Economic Features of Age-Related Neurological Diseases  19

2.1     Introduction  19

2.2     Parkinson's Disease  19

2.3     Amyotrophic Lateral Sclerosis  29

2.4     Alzheimer's Disease  40

2.5     Summary of the Data on the Progressive, Age-Related Neurological Diseases  47

2.6     Neural Loci and Mechanisms of Action  48

        Endnote  49

3  Spectrums of Neurological Disease, Clusters, and Ubiquity  51

3.1     Introduction  51

3.2     Spectrums of Neurological Disease  51

3.3     The Dimension of the Problem when Assessing Potential Causal Factors in Neurological Diseases  54

3.4     Neurological Disease Clusters  57

3.5     Ubiquity  60

3.6     Nested Complex Systems: Proximal versus Distal Events as They May Relate to Neurological Diseases  60

3.7     The Path to "Curing" Neurological Diseases  63

4  Complexity, Cascading Failures, and Neurological Diseases  67

4.1     Introduction  67

4.2     Introduction to Complexity Theory and Complex Systems  67

4.3     Computer Programs and Computer Crashes  69

4.4     Biosemiosis in the CNS (Part 1)  70

4.5     Complexity in the CNS and the Impact of Genetic and Environmental Insults  73

4.6     Tipping Points and Time Lines of Disease Progression  77

5       Genetic Determinants of Neurological Disease  79

5.1     Introduction  80

5.2     Causality versus Coincidence  80

5.3     Actions of Mutant Genes in Neurological Disease  82

5.4     Genetic Mutations Linked to Parkinson's Disease  84

5.5     Genetic Mutations Linked to ALS  86

5.6     Genetic Mutations Linked to Alzheimer's Disease  92

5.7     Genes and Neurological Disease: Some General Considerations  94

6  Environmental Determinants of Neurological Disease and Gene-Toxin Interactions  97

6.1     Introduction  98

6.2     Toxins and Neurological Diseases  98

6.3     Aluminum and Neurological Disease  101

6.4     Single- vs. Multiple-Hit Models of Neurological Disease: Gene-Toxin Interactions  114

6.5     Genetic Susceptibility Factors  117

6.6     Biosemiosis (Part 2)  123

6.7     Gene-Toxin Interactions and Cascading Failures  124

6.8     Genes and Toxins in Neurological Disease: Penultimate Thoughts  124

6.9     And, Finally, the Microbiome  125

        Endnote  125

7  The Mystery and Lessons of ALS-PDC  127

7.1     Introduction  127

7.2     Neurological Disease Clusters and ALS-PDC  128

7.3     History and Features of ALS-PDC  129

7.4     Cycad and ALS-PDC  135

7.5     Amino Acid Toxins in Cycad and ALS-PDC  140

7.6     Non-Amino Acid Toxins Linked to ALS-PDC  143

7.7     Aluminum and Ionic Etiologies for ALS-PDC  147

7.8     Still Other Molecules Causal to ALS-PDC  148

7.9     What is the Current View on the Importance of ALS-PDC?  148

7.10    Complexity of Neurological Diseases as Viewed from Guam  151

        Endnote  151

Part II   Age and Time Lines of Neurological Disease  153

8  Neurological Disease Models and their Discontents: Validity, Replicability, and the Decline Effect  155

8.1     Introduction  155

8.2     Modeling Human Neurological Diseases: Possibilities and Pitfalls  156

8.3     Considerations Regarding Model Systems  158

8.4     Model Systems and their Discontents  159

8.5     Is There an Ideal Model for Studying Neurological Diseases? General Considerations  168

8.6     Specific Considerations for Ideal Model-System Approaches in ALS  170

8.7     Alternative Views of Neurological Disease and Model-Systems Approaches: Multiple-Hit Etiologies  172

9  The Progression and the Time Line of Neurological Disease  175

9.1     Introduction  175

9.2     Creating Disease Time Lines: The Framingham Study  176

9.3     Time Lines of Neurological Disease  176

9.4     Back to a Multiple-Hit Disease Consideration  180

9.5     Haecceity and Quiddity in Context to Biosemiosis and Multiple Hits  181

9.6     Some Final Thoughts on Time Lines of Neurological Disease: Differentiation and Neurogenesis  182

        Endnote  183

10  Development, Aging, and Neurological Disease  185

10.1    Introduction  185

10.2    The Fetal Basis of Adult Disease Hypothesis  186

10.3    ASD as a Developmental Neurological Disorder  188

10.4    Toxins and Developmental CNS Disorders  193

10.5    Developmental versus Mature CNS Disorders  193

        Endnotes  194

Part III  Interactions and Synergies in Neurological Disease  195

11  CNS-Immune System Interactions and Autoimmunity  197

11.1    Introduction  198

11.2    Immunity and the CNS, an Introduction to a Complex Topic  198

11.3    CNS-Immune System Interactions: More Detailed Considerations  202

11.4    Autoimmunity  205

11.5    Immune System Signaling Errors and Autoimmunity in ASD and Other Neurological Disorders  208

11.6    Laterality and Autoimmunity in Neurological Diseases  212

11.7    Other System Disorders in Neurological Diseases: More Evidence for Autoimmunity?  215

11.8    Are There Infectious Disease Links to Neurological Diseases?  215

12  The Impact of Synergy of Factors in Neurological Disease  219

12.1    Introduction  219

12.2    Synergistic and Additive Effects in General and as Applied to CNS Diseases  219

12.3    Gene-Environment (Toxin) Interactions in Non-neuronal Systems  221

12.4    Gene-Environment (Toxin) Interactions in Neurological Disease  224

12.5    Levels of Complexity in Gene-Toxin Interactions: Implications for Current and Future Therapeutics  226

Part IV  Transition and Politics in Neurological Disease  229

13  The Current Status of Neurological Disease Treatments  231

13.1    Introduction  231

13.2    Current Therapeutic Approaches to Treating Neurological Diseases  232

13.3    Summary  242

        Endnote  243

14  The Future of Translational Research in Neurological Disease  245

14.1    Introduction  245

14.2    Comparing Traumatic Brain Injury to Neurological Diseases  246

14.3    ALS and Polio: Comparing the Nature of Neural Degeneration and Progression in the Two Diseases  249

14.4    Neurological Diseases as Spectrum Disorders: Implications for Therapy  252

14.5    Cystic Fibrosis and Gene Therapy  254

14.6    Restoring CNS Function: What Is the Bottom Line?  255

14.7    Biosemiosis (Part 3) and True Narrative Representations  255

15  Defining the Limits for Neurological Disease Treatments  259

15.1    Introduction  259

15.2    The Complexity of the Human CNS versus One View of the Philosophy of Science  260

15.3    Examples of Unique Individuality: From Pilgrimages to Nature  261

15.4    Therapeutic Windows for the Treatment of Neurological Diseases  266

        Endnotes  270

16  The Politics and Economics of Neurological Disease  271

16.1    Introduction  271

16.2    The Problems with Single-Hit Models of Neurological Disease  272

16.3    Summarizing the Main Themes by Chapter  274

16.4    Can the Amount of Money Spent Change these Outcomes for Neurological Disease Treatment?  276

16.5    General Considerations for the Future of Neurological Disease Research  280

16.6    The Advent of Modern Dentistry and Dental Prophylaxis  284

16.7    Addressing Neurological Diseases at the Individual and Population Levels  286

Endnotes  290

Glossary 291

References  301

Index  355