Читать книгу Spectrums of Amyotrophic Lateral Sclerosis - Группа авторов - Страница 2
ОглавлениеTable of Contents
1 Cover
6 Foreword
7 Preface
9 CHAPTER 1: Clinical Heterogeneity of ALS – Implications for Models and Therapeutic Development INTRODUCTION CLINICAL HETEROGENEITY OF ALS PLEIOTROPY OF ALS GENES GENETIC MODELS TO STUDY ALS CONCLUSION CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
10 CHAPTER 2: Genetic Basis of ALS INTRODUCTION GENES CAUSING ALS RECENTLY DISCOVERED GENES ASPECTS OF ALS HERITABILITY NONCODING VARIATION CONCLUSIONS ACKNOWLEDGMENTS CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
11 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 EPIGENETIC MECHANISMS IN sALS MODIFICATIONS TO THE EPIGENOME BY ENVIRONMENTAL FACTORS CONCLUSION CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
12 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 REFERENCES
13 CHAPTER 5: The Microbiome of ALS – Does It Start from the Gut? INTRODUCTION RECENT STUDIES HOW COULD THE MICROBIOME CONTRIBUTE TO ALS? MICROBIOME MODULATION AS A POTENTIAL THERAPEUTIC AVENUE CONCLUSION CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
14 CHAPTER 6: Protein Aggregation in Amyotrophic Lateral Sclerosis INTRODUCTION PATHOLOGICAL PROTEIN INCLUSIONS ASSOCIATED WITH ALS CONSEQUENCES OF PROTEIN AGGREGATION IN ALS THE PRIMARY AGGREGATING PROTEINS IN ALS PRION‐LIKE PROPAGATION OF PROTEIN AGGREGATION IN ALS CONCLUSION ACKNOWLEDGMENTS CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
15 CHAPTER 7: Evidence for a Growing Involvement of Glia in Amyotrophic Lateral Sclerosis INTRODUCTION NON‐NEURONAL CELLS PLAY IMPORTANT ROLES IN NEURODEGENERATION INCLUDING IN ALS GLIAL ACTIVATION IN ALS MODELS GLIAL INCLUSION FORMATION IN ALS 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
16 CHAPTER 8: Animal Models of ALS – Current and Future Perspectives INTRODUCTION THE CLINICAL MANIFESTATIONS OF ALS CURRENT AND EXPERIMENTAL PHARMACOLOGICAL INTERVENTIONS CAUSATIVE FACTORS IN THE DEVELOPMENT OF ALS ANIMAL MODELS OF ALS FUTURE MODEL DEVELOPMENT ACKNOWLEDGMENTS CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
17 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 PHASE II TRIAL “PARADOX” PATIENT RECRUITMENT AND RETENTION ASSUMPTIONS FOR LEAD‐IN PHASES NAVIGATING REGULATORY NUANCES FUTURE DIRECTIONS ADVANCES IN DISEASE UNDERSTANDING AND ASSESSMENT NEW APPROACHES TO TRIAL DESIGN EDUCATION PEOPLE MAKE OR BREAK A TRIAL ACKNOWLEDGMENTS CONFLICT OF INTEREST COPYRIGHT AND PERMISSION STATEMENT REFERENCES
18 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
19 Index
List of Tables
1 Chapter 1TABLE 1.1 Spectrum of clinical disease phenotypes associated with genetic var...
2 Chapter 5TABLE 5.1 Summary of key findings linking ALS and the microbiome.
3 Chapter 9TABLE 9.1 Common adaptive trial designs.
List of Illustrations
1 Chapter 2FIGURE 2.1 Timeline of ALS gene discovery and the rate of genetically explai...
2 Chapter 3FIGURE 3.1 Risk factors in proposed etiologies for sALS. Susceptibility gene...
3 Chapter 4FIGURE 4.1 People with lytico (ALS) and bodig (PDC) on Guam. (a) A woman bed...FIGURE 4.2 (a) Decline by birth year in the numbers of newly diagnosed ALS, ...FIGURE 4.3 Pedigrees of four typical, unrelated families of Umatac village i...FIGURE 4.4 Cycad tree (Cycas micronesica K.D. Hill) on Guam.FIGURE 4.5 Venn diagram showing suggested interactions of genes and toxicant...
4 Chapter 5FIGURE 5.1 Main hypotheses explaining the role of the microbiome in ALS. The...
5 Chapter 6FIGURE 6.1 Schematic of protein misfolding and aggregation process and the a...
6 Chapter 7FIGURE 7.1 Schematic of the time course of how glial cells have been reporte...
7 Chapter 9FIGURE 9.1 Platform trials allow the evaluation of multiple therapies under ...FIGURE 9.2 Platform trials reduce the number of participants assigned to the...
Pages
1 iii
2 iv
3 v
4 xiii
5 xiv
6 xv
7 xvii
8 xviii
9 xix
10 xxi
11 1
12 2
13 3
14 4
15 5
16 6
17 7
18 8
19 9
20 10
21 11
22 12
23 13
24 14
25 15
26 16
27 17
28 18
29 19
30 20
31 21
32 22
33 23
34 24
35 25
36 26
37 27
38 28
39 29
40 30
41 31
42 32
43 33
44 34
45 35
46 36
47 37
48 38
49 39
50 40
51 41
52 42
53 43
54 44
55 45
56 46
57 47
58 48
59 49
60 50
61 51
62 52
63 53
64 54
65 55
66 56
67 57
68 58
69 59
70 60
71 61
72 62
73 63
74 64
75 65
76 66
77 67
78 68
79 69
80 70
81 71
82 72
83 73
84 74
85 75
86 76
87 77
88 78
89 79
90 81
91 82
92 83
93 84
94 85
95 86
96 87
97 88
98 89
99 90
100 91
101 92
102 93
103 94
104 95
105 96
106 97
107 98
108 99
109 100
110 101
111 102
112 103
113 105
114 106
115 107
116 108
117 109
118 110
119 111
120 112
121 113
122 114
123 115
124 116
125 117
126 118
127 119
128 120
129 121
130 123
131 124
132 125
133 126
134 127
135 128
136 129
137 130
138 131
139 132
140 133
141 134
142 135
143 136
144 137
145 138
146 139
147 140
148 141
149 142
150 143
151 144
152 145
153 146
154 147
155 148
156 149
157 150
158 151
159 152
160 153
161 154
162 155
163 156
164 157
165 158
166 159
167 160
168 161
169 162
170 163
171 164
172 165
173 166
174 167
175 168
176 169
177 170
178 171
179 172
180 173
181 174
182 175
183 176
184 177
185 178
186 179
187 180
188 181
189 182
190 183
191 184
192 185
193 186
194 187
195 188
196 189
197 190
198 191
199 192
200 193
201 194
202 195
203 196
204 197
205 198
206 199
207 201
208 202
209 203
210 204
211 205
212 206
213 207
214 208
215 209
216 210
217 211
218 212
219 213
