Disease Pathways : An Atlas of Human Disease Signaling Pathways

Disease Pathways: An Atlas of Human Disease Signaling Pathways is designed to fill a void of illustrated reviews about the cellular mechanisms of human diseases. It covers 42 of the most common non-oncologic diseases and illustrates the connections between the molecular causes of the disease and its symptoms. This resource provides readers with detailed information about the disease molecular pathways, while keeping the presentation simple. Pathway models that aggregate the knowledge about protein–protein interactions have become indispensable tools in many areas of molecular biology, pharmacology, and medicine. In addition to disease pathways, the book includes a comprehensive overview of molecular signaling biology and application of pathway models in the analysis of big data for drug discovery and personalized medicine. This is a must-have reference for general biologists, biochemists, students, medical workers, and everyone interested in the cellular and molecular mechanisms of human disease. Key Features Over 145 full-color illustrations of the molecular and cellular cascades underlying the disease pathology. Disease pathways are based on computational models from Elsevier’s Disease Pathway Collection, published for the first time outside of Pathway Studio® commercial software. Each relationship on the pathway models is supported by references to scientific articles and can be examined at freely available online resources. Readership Endocrinologists, neurologists, cardiologists, immunologists, molecular biologists, geneticists, biochemists, students, and researchers who require information to understand cellular and molecular mechanisms of human diseases Front Cover......Page 1 Disease Pathways: An Atlas of Human Disease Signaling Pathways......Page 4 Copyright......Page 5 Contents......Page 6 Contributors......Page 16 Foreword: The future of medical discovery......Page 18 Preface......Page 20 Intended audience......Page 21 Guide and legend......Page 22 Part I Introduction......Page 30 Terminology of cellular systems......Page 32 Signal reception......Page 35 Signal transduction inside the cell......Page 38 Cell response......Page 39 Major signaling pathways......Page 40 Diverse definitions and concepts of systems biology......Page 43 Pathways as objects for analysis in systems biology......Page 44 Pathways ontology and disease pathways......Page 52 Reconstruction of disease pathways described in the book......Page 55 References......Page 57 Part II Human disease pathways......Page 62 Chapter 2 Infectious diseases......Page 64 Chapter 2.1 Human immunodeficiency virus (HIV) and Łacquired immunodeficiency syndrome (AIDS)......Page 66 Outcome effects......Page 69 Transport to the nucleus and viral integration......Page 70 Viral reproduction......Page 71 Outcome effects......Page 73 Signaling......Page 74 Low level of viral production ( Fig. 3)......Page 77 Postintegration latency ( Fig. 4)......Page 78 References......Page 82 Chapter 2.2 Human T-cell leukemia virus infection and leukemia progression......Page 84 Signaling......Page 87 Signaling......Page 89 Signaling......Page 92 Signaling......Page 94 Signaling......Page 97 Signaling......Page 100 References......Page 102 Chapter 2.3 Human papillomavirus infection and cancer......Page 104 Signaling......Page 107 Signaling......Page 110 Signaling......Page 113 Signaling......Page 116 Signaling......Page 119 References......Page 122 Chapter 3 Diseases of the blood......Page 124 Chapter 3.1 Anemia of chronic disease (inflammatory anemia)......Page 126 Signaling......Page 129 Signaling......Page 131 Signaling......Page 134 Signaling......Page 136 Signaling......Page 138 References......Page 140 Chapter 3.2 Hemophilia......Page 141 Coagulation cascade ( Fig. 6)......Page 145 Feedback relations between coagulation and fibrinolysis ( Fig. 7)......Page 146 References......Page 147 Chapter 4 Endocrine, nutritional, and metabolic diseases......Page 150 Chapter 4.1 Diabetes mellitus type I......Page 153 Signaling......Page 157 Inducing signals......Page 160 Signaling......Page 161 Signaling......Page 164 References......Page 167 Chapter 4.2 Type 2 diabetes mellitus......Page 169 Signaling......Page 173 Insulin processing and storage ( Fig. 4)......Page 174 Insulin secretion ( Fig. 5)......Page 175 Signaling......Page 178 Proliferation ( Fig. 7)......Page 181 Neogenesis/dedifferentiation ( Fig. 8)......Page 182 Recovery ( Fig. 9)......Page 183 Outcome effects......Page 188 Inflammation-related insulin resistance ( Fig. 11)......Page 189 FFA-related insulin resistance ( Fig. 12)......Page 190 References......Page 195 Chapter 4.3 Diabetic neuropathy......Page 198 Signaling......Page 201 Signaling......Page 204 Signaling......Page 207 References......Page 210 Chapter 4.4 Hypothyroidism......Page 211 Thyrotropin-releasing hormone......Page 214 Thyroid stimulating hormone......Page 215 TSHR signaling and thyroid follicle cells......Page 216 Hashimoto’s thyroiditis......Page 217 General pathways of thyroid hormone signaling ( Fig. 17)......Page 219 Cell-specific effects of thyroid hormone action ( Fig. 18)......Page 220 References......Page 226 Chapter 4.5 Alpha-1 antitrypsin deficiency......Page 228 Signaling......Page 230 Signaling......Page 233 References......Page 235 Chapter 4.6 Cystic fibrosis......Page 236 Signaling......Page 239 Outputs......Page 242 Mucus production......Page 243 Oxidative stress......Page 244 References......Page 246 Chapter 5 Diseases of the nervous system......Page 248 Chapter 5.1 Alzheimer’s disease......Page 250 Signaling......Page 253 References......Page 260 Chapter 5.2 Amyotrophic lateral sclerosis......Page 263 Signaling......Page 266 Signaling......Page 269 References......Page 273 Chapter 5.3 Familial hemiplegic migraine (FHM)......Page 275 NO and PGH2 synthesis in neuronal tissue ( Fig. 5)......Page 278 NO-mediated vasodilation ( Fig. 6)......Page 279 Outcome effects......Page 282 Signaling......Page 283 References......Page 286 Chapter 6 Diseases of the eye......Page 288 Chapter 6.1 Glaucoma......Page 290 Signaling......Page 293 Signaling......Page 296 Signaling......Page 298 References......Page 300 Chapter 6.2 Age-related macular degeneration......Page 302 Signaling......Page 305 Signaling......Page 307 Signaling......Page 310 References......Page 312 Chapter 6.3 Cataract......Page 314 Signaling......Page 316 Signaling......Page 319 Signaling......Page 321 References......Page 324 Chapter 7 Diseases of the ear......Page 326 Chapter 7.1 Hearing loss......Page 328 Signaling......Page 331 Signaling......Page 335 Signaling......Page 338 References......Page 341 Chapter 7.2 Otitis media......Page 344 Signaling......Page 347 Signaling......Page 350 References......Page 353 Chapter 8 Diseases of the circulatory system......Page 356 Chapter 8.1 Atherosclerosis description......Page 359 Signaling......Page 362 The first mechanism is NO and ROS production......Page 365 The third mechanism is ECM remodeling......Page 366 Signaling......Page 369 References......Page 372 Chapter 8.2 Hypertension......Page 374 Signaling......Page 377 Signaling......Page 380 Signaling......Page 383 Signaling......Page 386 References......Page 389 Chapter 8.3 Pulmonary arterial hypertension......Page 390 Signaling......Page 393 Signaling......Page 396 Signaling......Page 399 References......Page 402 Chapter 8.4 Hypertrophic cardiomyopathy......Page 403 Signaling......Page 405 Signaling......Page 408 References......Page 410 Chapter 8.5 Arrhythmogenic right ventricular dysplasia (ARVD)......Page 411 Signaling......Page 413 Signaling......Page 415 Signaling......Page 417 References......Page 419 Chapter 9 Diseases of the respiratory system......Page 420 Chapter 9.1 Asthma......Page 422 Key cellular contributors and processes......Page 424 Outputs......Page 426 Antigen-presenting cells in asthma......Page 427 IgE antibodies production......Page 428 Outcome effects......Page 431 Eosinophil migration and activation (Fig. 2)......Page 432 Eosinophil apoptosis (Fig. 4)......Page 433 Neutrophil chemotaxis and activation (Fig. 4)......Page 434 Outcome effects......Page 438 Mucins release (Fig. 5)......Page 439 Regulation of airway surface liquid thickness (Fig. 6)......Page 440 Airway smooth muscle cell contraction (Fig. 7)......Page 444 ASM proliferation and airway tissue remodeling (Fig. 8)......Page 445 References......Page 449 Chapter 9.2 Chronic obstructive pulmonary disease......Page 454 Key cellular contributors and processes......Page 456 Signaling......Page 459 Signaling......Page 462 Signaling......Page 465 Signaling......Page 468 References......Page 470 Chapter 10 Diseases of the digestive system......Page 472 Chapter 10.1 Crohn’s disease......Page 474 Incoming signals......Page 478 Signaling......Page 479 Signaling......Page 482 Signaling......Page 484 References......Page 486 Chapter 10.2 Ulcerative colitis......Page 488 Outcome effects......Page 491 Cell-to-cell junctions......Page 492 Short-chain fatty acids......Page 493 Signaling......Page 495 Signaling......Page 498 Polymorphisms associated with inflammatory bowel diseases ( Fig. 7)......Page 500 References......Page 503 Chapter 10.3 Celiac disease......Page 505 Signaling......Page 507 Signaling......Page 510 References......Page 512 Chapter 10.4 Nonalcoholic fatty liver disease......Page 513 Signaling......Page 515 Signaling......Page 518 References......Page 520 Chapter 11 Diseases of the skin and subcutaneous tissue......Page 522 Chapter 11.1 Acne vulgaris......Page 524 Signaling......Page 526 Signaling......Page 528 Signaling......Page 530 References......Page 532 Chapter 11.2 Atopic dermatitis......Page 533 Signaling......Page 537 Outcome effects......Page 539 Signaling......Page 540 References......Page 542 Chapter 11.3 Psoriasis......Page 543 Signaling......Page 545 Signaling......Page 548 References......Page 551 Chapter 11.4 Ichthyosis......Page 552 Signaling......Page 554 Signaling......Page 556 Signaling......Page 559 References......Page 561 Chapter 12 Diseases of the musculoskeletal system......Page 562 Chapter 12.1 Osteoarthritis......Page 564 Signaling......Page 567 Signaling......Page 570 Signaling......Page 573 References......Page 576 Chapter 12.2 Osteoporosis (type I)......Page 577 Signaling......Page 579 Signaling......Page 582 References......Page 585 Chapter 12.3 Osteopetrosis......Page 586 Signaling......Page 588 Signaling......Page 592 Signaling......Page 594 References......Page 596 Chapter 13 Diseases of the genitourinary system......Page 598 Chapter 13.1 Pyelonephritis......Page 601 Signaling......Page 604 Signaling......Page 606 Signaling......Page 608 References......Page 610 Chapter 13.2 Glomerulonephritis......Page 611 Signaling......Page 615 Signaling......Page 617 Signaling......Page 620 References......Page 622 Chapter 13.3 Polycystic kidney disease......Page 623 Signaling......Page 626 Signaling......Page 629 References......Page 631 Chapter 13.4 Polycystic ovary syndrome......Page 632 Signaling......Page 635 Signaling......Page 638 References......Page 641 Chapter 13.5 Endometriosis......Page 642 Signaling......Page 645 Signaling......Page 648 Signaling......Page 651 References......Page 653 Part III Pathway analysis perspectives/advantages......Page 656 Chapter 14 Applications of disease pathways in biology and medicine......Page 658 Pathway analysis for personalized medicine......Page 661 Bioinformatics foundation for patient data analysis......Page 665 Gene grouping techniques......Page 666 Pathway analysis as a part of functional enrichment analysis......Page 669 Pathway topology–based enrichment analysis......Page 672 Network-based enrichment analysis......Page 674 Pathway and network analysis output interpretation......Page 677 In silico modeling in biomedicine......Page 681 Pathway collections and network databases......Page 685 Software and tools......Page 687 Conclusion......Page 688 References......Page 689 Glossary and index......Page 698 Links......Page 710 Index......Page 716 Back Cover......Page 734

Disease Pathways: An Atlas of Human Disease Signaling Pathways is designed to fill a void of illustrated reviews about the cellular mechanisms of human diseases. It covers 42 of the most common non-oncologic diseases and illustrates the connections between the molecular causes of the disease and its symptoms. This resource provides readers with detailed information about the disease molecular pathways, while keeping the presentation simple.

Pathway models that aggregate the knowledge about protein–protein interactions have become indispensable tools in many areas of molecular biology, pharmacology, and medicine. In addition to disease pathways, the book includes a comprehensive overview of molecular signaling biology and application of pathway models in the analysis of big data for drug discovery and personalized medicine.

This is a must-have reference for general biologists, biochemists, students, medical workers, and everyone interested in the cellular and molecular mechanisms of human disease.

• Over 145 full-color illustrations of the molecular and cellular cascades underlying the disease pathology.
• Disease pathways are based on computational models from Elsevier’s Disease Pathway Collection, published for the first time outside of Pathway Studio® commercial software.
• Each relationship on the pathway models is supported by references to scientific articles and can be examined at freely available online resources.