Human Brain Proteome (eBook)

Cover 1
Title Page 4
Copyright Page 5
Contents 6
Contents of Recent Volumes 338
Contributors 10
SECTION I: HIGH-THROUGHPUT TECHNOLOGIES 14
Chapter 1. Biomarker Discovery Using Molecular Profiling Approaches 16
I. Introduction 16
II. Transcriptomics 17
III. Proteomics Methodologies for Biomarker Discovery 20
IV. Principles of SELDI-TOF-MS 25
V. SELDI-TOF-MS in Clinical Proteomics Research 30
VI. Biomarkers in Specific Diseases 31
VII. Metabolomics 38
VIII. Conclusions 39
References 40
Chapter 2. Proteomic Analysis of Mitochondrial Proteins 44
I. Introduction 44
II. Model Systems 45
III. Technological Approaches 46
IV. Differential Expression of Proteins in Mouse Brain Mitochondria from Cortex and Synaptosomes. 51
V. Conclusions 56
References 57
SECTION II: PROTEOMIC APPLICATIONS 62
Chapter 3. NMDA Receptors, Neural Pathways, and Protein Interaction Databases 64
I. Introduction 64
II. NMDA Receptor 65
III. Molecular Clustering 68
IV. Signal Transduction Pathways 74
VI. Proteomic Databases 80
VII. Future Directions 86
References 87
Chapter 4. Dopamine Transporter Network and Pathways 92
I. Introduction 92
II. Structure and Function of DAT 93
III. Cellular Localization of DAT 94
IV. Regulation of DAT 94
V. Mass Spectrometry-Based Proteomics 96
VI. Isolation and Validation of the DAT Protome 97
VII. Mass Spectrometry 98
VIII. Confirmation of Members of the DAT Proteome 98
IX. In Silico Analysis of DAT Proteome 103
References 106
Chapter 5. Proteomic Approaches in Drug Discovery and Development 110
I. Proteomics in Drug Discovery and Development 110
II. Using Proteomics to Identify Biomarkers of Alzheimer’s Disease: A Case Study 117
III. Future Challenges and Conclusions 133
References 134
SECTION III: INFORMATICS 140
Chapter 6. Proteomic Informatics 142
I. What is Proteomics? 142
II. Proteomic Informatics 144
III. Mass Spectrometry and Shotgun Proteomics 144
IV. Identifying Proteins 147
V. Post-hoc Validation of Protein Identification Program Output 152
VI. Quantification 154
VII. Detection of Protein Isoforms 155
VIII. Systems and Workflow Issues 159
IX. Conclusion 163
X. Appendix: List of Mentioned Algorithms by Topic 163
References 167
SECTION IV: CHANGES IN THE PROTEOME BY DISEASE 172
Chapter 7. Proteomics Analysis in Alzheimer’s Disease: New Insights into Mechanisms of Neurodegeneration 174
I. Introduction 174
II. Proteomics Tools 175
III. Proteomic Studies in AD 183
IV. Proteomics Analysis of Transgenic Models of AD 194
V. Future of Proteomics in AD 195
References 195
Chapter 8. Proteomics and Alcoholism 202
I. Introduction 202
II. Proteomics of the Hippocampus and Nucleus Accumbens 205
III. Future Directions 216
IV. Conclusion 224
References 224
Chapter 9. Proteomics Studies of Traumatic Brain Injury 228
I. Introduction 228
II. Traumatic Brain Injury 229
III. Proteomics Analysis Overview 234
IV. Protein Separation Methods 234
V. Protein Identification and Quantification Methods 238
VI. TBI Proteomics Bioinformatics 245
VII. Prospective Utilities of TBI Proteomics Data 250
References 250
Chapter 10. Influence of Huntington’s Disease on the Human and Mouse Proteome 254
I. Introduction 254
II. Neurodegenerative Disorders Caused by Elongated Poly-Glutamine Repeats 255
III. Approach for an HD Proteomics Study 261
IV. Materials and Methods 261
V. Proteomics Study of HD 262
VI. Discussion 283
VII. Conclusion 290
References 291
SECTION V: OVERVIEW OF THE NEUROPROTEOME 298
Chapter 11. Proteomics„Application to the Brain 300
I. Introduction 300
II. Potential of Proteomics 301
III. Methods in Proteome Analysis 302
IV. Proteome Analysis in Neurosciences 312
V. Administrative Realization of Neuroproteomics 316
References 320
Index 326