Most neurodegenerative diseases have animal parallels such as Alzheimers in chimpanzees, multiple sclerosis in macaques, Lou Gehrigs disease in dogs, but nothing like Parkinsons has ever been seen in any species but humans. Synuclein and the Coelacanth: The Molecular and Evolutionary Origins of Parkinson's Disease delves into the causes of Parkinsons disease and how the evolution of the human brain has left us uniquely vulnerable. Genetic risk factors, environmental toxins, and neuroanatomy are woven together in a multidisciplinary discussion that ranges from subatomic physics to socioeconomics. Connections between neurodegenerative disease, neural pathways, and innate immunity are explored. Finally, the author discusses new therapeutic agents are being developed that hope to go beyond just treating the symptoms of Parkinsons and actually halt the disease.
- Proposes a new hypothesis on the origins of Parkinsons disease
- Examines genetic risk factors, environmental toxins, and neuroanatomy of PD
- Highlights new therapeutic treatment options in development for patients
| Preface |
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ix | |
| Acknowledgements |
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xi | |
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1 Out of the Depths - The synuclein proteins, their evolution, and the genetic code |
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1 | (10) |
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10 | (1) |
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2 Bad News, Good News -- The demographics and genetic and environmental risk factors for Parkinson's disease |
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11 | (22) |
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31 | (2) |
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3 The Family Tremor -- REM sleep behaviour disorder and essential tremor |
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33 | (16) |
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46 | (3) |
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4 The Knockout -- The history of the knockout mouse and the surprising results for the synuclein proteins |
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49 | (20) |
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67 | (2) |
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5 Shapeshifter -- The molecular structure and normal biological role of synuclein in neurons |
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69 | (20) |
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The nuclei sing -- NMR spectroscopy |
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76 | (10) |
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86 | (3) |
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6 A New Kind of Pathogen - Prion diseases and amyloid fibrils |
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89 | (24) |
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Crop rows -- X-ray crystallography |
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99 | (5) |
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Ghost in the static - Cryo-EM |
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104 | (4) |
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108 | (5) |
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7 Addicts -- Neurotoxins that cause parkinsonism and the search for analogues in the environment |
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113 | (16) |
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126 | (3) |
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8 Attack of the Oligomers -- Alpha-synuclein amyloid oligomers and their pathogenic roles |
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129 | (1) |
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Part 1 Unmasking the villain |
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129 | (8) |
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Twisting light -- CD spectroscopy |
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134 | (3) |
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Part 2 Mitochondria, the scene of the crime |
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137 | (9) |
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Part 3 Alpha-synuclein mutants, the final mystery |
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146 | (125) |
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154 | (5) |
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9 An Evolutionary Affair -- The connection between Gaucher disease and Parkinson's disease |
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159 | (22) |
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Are we related? -- Correlated mutation analysis |
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166 | (12) |
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178 | (3) |
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10 Monkey Brains -- Evolution of the human brain and the vulnerability of the substantia nigra |
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181 | (12) |
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190 | (3) |
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11 A Troublesome Subject - Exploring the possible connection between intelligence and Parkinson's and Alzheimer's diseases |
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193 | (16) |
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206 | (3) |
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12 Appendix -- Alpha-synuclein in the gut, Crohn's disease, and the possible protective role of the synucleins in innate immune response |
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209 | (18) |
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224 | (3) |
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13 Circuitry--The discovery of neural pathways involved in Parkinson's disease and deep brain stimulation |
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227 | (16) |
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240 | (3) |
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14 Seeking a Magic Bullet--the search for new Parkinson's disease therapeutic agents |
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243 | (18) |
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No financial gain, there will be paine--Ethics at NIH |
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248 | (9) |
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257 | (4) |
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15 Journey's End - A recap of the chapters, the final conclusions, and new directions to explore |
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261 | (10) |
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270 | (1) |
| Glossary |
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271 | (20) |
| Index |
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291 | |
James M. Gruschus is a molecular biophysicist with a Ph.D. in physics from Cornell University. He is currently employed as a staff scientist in the Laboratory of Structural Biophysics, National Heart, Lung & Blood Institute, National Institutes of Health, Bethesda, MD, and resides in Washington, DC.
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