Inflammasome Biology

Fundamentals, Role in Disease States, and Therapeutic Opportunities

1st Edition - November 23, 2022
Imprint: Academic Press
Editor: Pablo Pelegrin
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 1 8 0 2 - 2
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 7 2 0 6 - 2

Inflammasome Biology: Fundamentals, Role in Disease States, and Therapeutic Opportunities is a complete reference on the role of inflammasomes in health and disease. Sections… Read more

Purchase options

BLOOM INTO SPRING SAVINGS

Save up to 25% on books and eBooks!

Shop now

Institutional subscription on ScienceDirect

Request a sales quote

Inflammasome Biology: Fundamentals, Role in Disease States, and Therapeutic Opportunities is a complete reference on the role of inflammasomes in health and disease. Sections cover the different types of inflammasomes, including cellular signaling, structural and evolutive aspects, overview the role of inflammasomes in key diseases, microbial infections and human body systems conditions, cover the interplay between Inflammasomes and cell death processes, and discuss current therapeutic opportunities driven by inflammasome research, including targeting, blocking and inhibiting the development of inflammasomes through both synthetic and natural compounds.

This book is the perfect reference for cell biologists, immunologists and research clinicians to understand the foundations of inflammasomes and explore the therapeutic opportunities they present. Pharma researchers may also find this reference invaluable in devising new approaches to developing anti-inflammatory drugs.

Cover image
Title page
Table of Contents
Copyright
Contributors
Section 1. Fundamentals of inflammasome biology
Chapter 1. The inflammatory process at the cellular level
1. Introduction
2. At the dawn of inflammation
3. Detection and integration of inflammatory signals
4. Inflammatory cells and inflammatory mediators
5. Inflammation is an energy-consuming process
6. Resolution (or lack of resolution) of inflammation
7. Conclusions
Chapter 2. Inflammasome formation and triggers
1. The inflammasome platform assembles in response to various triggers
2. Inflammasome sensors predominantly belong to NLR and ALR receptor families
3. Adaptor ASC augments inflammation
4. Caspase-1 processes proinflammatory cytokines and gasdermin D
5. NLRP3 inflammasome
6. NAIP/NLRC4 inflammasome
7. NLRP6 inflammasome
8. NLRP1 inflammasome
9. CARD8 inflammasome
10. AIM2 inflammasome
11. Pyrin inflammasome
12. Conclusions
Chapter 3. The NLRP1 and CARD8 inflammasomes
1. NLRP1 and CARD8 domain architecture
2. NLRP1 and CARD8 activation by proteolytic cleavage
3. NLRP1 activation by pathogen-associated E3 ligases
4. Activation of NLRP1 by dsRNA
5. Activation of NLRP1 through ATP depletion
6. NLRP1 recognition of Toxoplasma infection
7. Regulation of NLRP1 by DPP8 and DPP9
8. Disease-associated mutations in NLRP1
9. Unresolved questions
Chapter 4. Cellular signaling, molecular activation, and regulation of the NLRP3 inflammasome
1. Introduction
2. NLRP3 priming
3. Canonical NLRP3 activation
4. Other pathways of NLRP3 activation
5. Conclusion
Chapter 5. Cellular signaling, molecular activation, and regulation of the NLRP6 inflammasome
1. Introduction
2. NLRP6 expression
3. NLRP6 activation
4. Inflammasome-dependent and inflammasome-independent functions of NLRP6
5. NLRP6 in host defense
6. NLRP6 in epithelial barrier integrity
7. NLRP6 and microbiota
8. NLRP6 in human diseases
9. Concluding remarks
Chapter 6. Molecular regulation of NAIP/NLRC4 inflammasomes
1. NAIP/NLRC4 inflammasomes
2. Molecular mechanisms involved in canonical NAIP/NLRC4 inflammasome assembly
3. Molecular mechanisms involved in the noncanonical activation of NAIP/NLRC4
4. Role of NAIP/NLRC4 in host defense against infections
5. Role of NLRC4 in inflammatory pathologies
6. NAIP/NLRC4 in cancer
7. Conclusions and future directions
Chapter 7. Cellular signaling, molecular activation, and regulation of the AIM2 inflammasome
1. Introduction
2. Mechanism of AIM2 inflammasome assembly
3. AIM2-mediated recognition of infection and self-DNA
4. Positive and negative regulation of the AIM2 inflammasome
5. Conclusions
Chapter 8. Molecular activation, cellular signaling, and regulation of the Pyrin inflammasome
1. Introduction
2. Pyrin structure
3. Pyrin is a guard of RhoA GTPases
4. Pyrin activation during bacterial infections
5. The regulation of Pyrin inflammasome
6. Pyrin in autoinflammatory diseases
7. Conclusions
Chapter 9. Cellular signaling, molecular activation, and regulation of the noncanonical inflammasome
1. Introduction
2. Noncanonical inflammasome activation
3. Cofactors regulating noncanonical inflammasome activation
4. Noncanonical inflammasome assembly
5. Alternative activation of the noncanonical inflammasome
6. Regulation and evasion of the noncanonical inflammasome
7. Concluding remarks
Chapter 10. Cellular signaling, molecular activation, and regulation of auto-active inflammasomes: Insights from disease-associated variants
1. Introduction
2. Protein structure
3. Pyrin-associated autoinflammatory disease
4. Familial Mediterranean fever
5. Pyrin-associated dominant diseases
6. Pyrin-associated complex diseases
7. NLR-associated diseases
8. NLRP1-associated diseases
9. NLRP3-associated diseases
10. NLRP3-germline variants–associated diseases
11. NLRP3-somatic variants–associated diseases
12. NLRP3-common variants–associated diseases
13. NLRC4-associated diseases
14. NLRP7-associated diseases
15. NLRP12-associated diseases
16. Conclusion
Chapter 11. Autophagy and the inflammasome
1. Introduction
2. Inflammasome
3. Autophagy
4. Autophagy modulates inflammasome activation
5. Sepsis
6. Conclusions and further directions
Chapter 12. Inflammasome effector functions: a Tale of Fire and Ice
1. Introduction
2. NLRP3
3. NLRP1
4. AIM2
5. NLRC4/NAIP
6. Conclusion
Chapter 13. Inflammatory caspases
1. Introduction
2. Domain structure of inflammatory caspases
3. CARD-mediated dimerization of caspase catalytic domains induces basal activity
4. Autoproteolytic cleavage of the interdomain linker yields fully active inflammatory caspases
5. Substrates recognition by inflammatory caspases
6. Regulation of inflammatory caspases on inflammasomes
7. Regulation of inflammatory caspases-1CARD filament formation
8. Concluding remarks
Chapter 14. Structural aspects of inflammasomes forming NOD-like receptors
1. Introduction
2. Inflammasome-forming NOD-like receptors
3. NOD-like receptors are STAND family ATPases
4. Sequence motifs in the NOD module
5. Domain composition and architecture of NOD-like receptors
6. Conformational states of NLRs from inactive to active
7. Structures of inactive inflammasomal proteins
8. Structure of active inflammasome-forming NLRs
9. Downstream effectors of the NLR nucleation seed
10. Conclusions
Chapter 15. Evolutive aspects of inflammasomes
1. Introduction
2. Evolution of inflammasome-related genes in mammals and teleosts
3. Functional evolution of the CASP1
4. Conclusions
Section 2. Inflammasome role in disease processes
Chapter 16. The inflammasome in cardiovascular diseases
1. Introduction
2. Atherosclerosis
3. Ischemic heart disease
4. Inflammatory heart disease
5. Dilated cardiomyopathy
6. Heart failure
7. Peripheral arterial disease and venous thromboembolism
8. Acute versus chronic cardiovascular diseases
9. Conclusions
Chapter 17. Inflammasome implications in metabolic disorders
1. Introduction
2. Obesity, diabetes, and related comorbidities
3. Atherosclerosis
4. Nonalcoholic fatty liver disease
5. Conclusions and future perspectives
Chapter 18. The inflammasome in stroke
1. Epidemiology, risk factors, and types of stroke
2. Stroke pathophysiology
3. Molecular events taking place after stroke
4. Inflammasome activation in stroke
5. Inflammasomes involved in the innate immune response after stroke
6. The inflammasome after stroke in humans
7. Therapeutic targeting of the inflammasome after stroke
8. Conclusions
Chapter 19. Inflammasome and neurodegenerative diseases
1. Introduction
2. Inflammasome, a double-edged sword
3. NLRP3, the predominant inflammasome
4. Inflammasome in Alzheimer's disease
5. Inflammasome activation in PD
6. Inflammasome activation in ALS
7. Conclusion
Chapter 20. Inflammasomes in cigarette smoke- or ozone-induced lung diseases
1. Introduction
2. Cigarette smoke–induced inflammation and COPD
3. Ozone-induced inflammation, COPD, and fibrosis
4. Conclusions
Chapter 21. Inflammasomes and their regulation in oral diseases
1. Introduction
2. Inflammasomes in periodontal disease
3. Inflammasome modulation in periodontal disease
4. Inflammasomes in pulpal diseases
5. Inflammasome modulation in pulpal diseases
6. Inflammasomes in oral cancer
7. Inflammasome modulation in oral cancer
8. Conclusion and future perspectives
Chapter 22. Inflammasome-induced inflammation and fibrosis in liver
1. The NLRP3 inflammasome in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
2. The NLRP3 inflammasome in alcoholic liver disease
3. The NLRP3 inflammasome in acetaminophen and toxin-induced acute liver failure
4. The NLRP3 inflammasome in autoimmune and viral hepatitis
5. The NLRP3 inflammasome in hepatocarcinogenesis
6. NLRP1, NLRP6, NLRC4, AIM2, and noncanonical inflammasome in liver disease
Chapter 23. Inflammasomes in sepsis
1. Introduction
2. Clinical consequences of sepsis and clinical management
3. Inflammatory response during sepsis
4. The role of inflammasomes in sepsis
5. Use of inflammasomes in the prognosis of septic patients
Chapter 24. The Inflammasome in viral, bacterial, and fungal infections
1. NLRP1 inflammasome in infection
2. Activation of CARD8 inflammasome by the human immunodeficiency virus
3. NLRP3 inflammasome activation in infection
4. NLRC4 inflammasome triggering during infections
5. Other NLRs in infection
6. AIM2 and pyrin inflammasomes during infection
7. The noncanonical inflammasome during infection
8. Concluding remarks
Chapter 25. Autoinflammatory disorders
1. Autoinflammation and monogenic human autoinflammatory disorders
2. Inflammasomopathies
3. IL-1-mediated, noninflammasome-related autoinflammatory disorders
4. Monogenic type I interferonopathies
5. Deficiency of adenosin deaminase 2 (DADA2)
6. Disorders associated with aberrant TNF or NF-κB signaling pathways
7. Inflammatory actinopathies
8. Others
Chapter 26. The inflammasome in graft-versus-host disease
Chapter 27. Canonical and noncanonical Inflammasomes in kidney disease
1. Introduction
2. Canonical inflammasome activation
3. Noncanonical inflammasome activation
4. Inflammasomes and kidney injury
5. Other inflammasomes in kidney injury
6. Conclusions
Chapter 28. Inflammasomes and cancer
1. Introduction
2. NLRP1 inflammasome and cancer
3. NLRP3 inflammasome and cancer
4. NLRP6 inflammasome and cancer
5. NLRP12 inflammasome and cancer
6. NLRC4 inflammasome and cancer
7. AIM2 inflammasome and cancer
8. Downstream effectors of inflammasomes and cancer
9. Therapeutic perspectives
10. Conclusions
Chapter 29. Inflammasomes in the pathobiology of degenerative retinopathies
1. The organization of the retina
2. The retinal immune system
3. Oxidative stress and the retina
4. Canonical and noncanonical inflammasomes
5. Age-related macular degeneration
6. Dry age–related macular degeneration and the inflammasome
7. Neovascular age–related macular degeneration and the inflammasome
8. The inflammasomes in diabetic retinopathy
9. Inherited retinal degenerations and the inflammasome
10. Therapeutic directions
Section 3. Inflammasome cross talk in cell death
Chapter 30. Regulation of pyroptosis by inflammasomes
1. Introduction
2. Gasdermin activation and gasdermin pore properties
3. Cytokines and alarmins release during pore formation and pyroptosis
4. Mechanisms to prevent GSDM-mediated pyroptosis
5. Gasdermin regulation by reactive oxygen species production
6. Gasdermin activation by other proteases
Chapter 31. Crosstalk between necroptosis and the inflammasome
1. Proteins that modulate necroptosis
2. Molecular mechanisms of necroptosis and necrosome formation
3. Interaction of necroptosis with the inflammasome
4. Importance of necroptosis and inflammasome crosstalk in mediating host responses to pathogens
5. Potential role for mitochondria in mediating necroptosis and inflammasome crosstalk
6. Conclusions
Chapter 32. Apoptosis and inflammasome regulation
1. Introduction
2. Extrinsic and intrinsic apoptosis pathways
3. Pyroptosis: programmed necrosis induced by inflammasomes and gasdermin family members
4. Links between apoptosis and pyroptosis
5. Conclusions and outlook
Chapter 33. Inflammasomes as integral components of PANoptosomes in the regulation of cell death
1. Introduction
2. Regulation of pyroptosis by inflammasomes
3. Inflammasomes at the junction of innate immune cell death crosstalk
4. Role of inflammasomes in PANoptosis
5. Implications of PANoptosis in disease treatment
6. Summary and remaining questions
Chapter 34. Regulation of neutrophil NETosis by inflammasome
1. Introduction
2. The inflammasome
3. NETosis mechanisms
4. NETosis and inflammasome in disease
5. NET-mediated inflammasome activation
6. Pharmacological inhibition of inflammasome-mediated NETosis
7. Conclusion and perspectives
Section 4. Therapeutic opportunities
Chapter 35. Therapeutic opportunities targeting the NLRP3 inflammasome
1. Inflammasomes as therapeutic targets
2. Targeting NLRP3 priming
3. Targeting NLRP3 activation
4. Targeting ASC, caspase-1, and gasdermin D
5. Targeting downstream effector functions
6. NLRP3 agonism
7. Conclusions
Chapter 36. Development of selective NLRP3 inflammasome inhibitors
1. Introduction
2. Sulfonylurea and sulfonylurea-derived NLRP3 inhibitors
3. Benzensulfonamide derivatives as NLRP3 inhibitors
4. Acrylic acid derivatives
5. Other chemotypes NLRP3 inhibitors
6. Concluding remarks and future perspectives
Chapter 37. Therapeutic targeting of inflammasome signaling by blocking interleukin-1
1. Introduction
2. Interleukin-1
3. IL-1 inhibitors
4. IL-1 receptor antagonism
5. IL-1 decoy receptors
6. Anti-IL-1 antibodies
7. Safety considerations for IL-1 blockers
8. Conclusions
Chapter 38. Multiinflammasome inhibitors
Author disclosures
1. Introduction
2. The structure of the ASC: necessary knowledge for the development of pan-inflammasome inhibitors
3. ASC modulation as a strategy for multiinflammasome inhibitors
4. Endogenous inflammasome modulators
5. Posttranslational modulation of ASC-mediated inflammasome activation
6. Therapeutic indications for multiinflammasome inhibitors
7. Conclusions
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Inflammasome Biology

Fundamentals, Role in Disease States, and Therapeutic Opportunities

Purchase options

BLOOM INTO SPRING SAVINGS

Institutional subscription on ScienceDirect

Pablo Pelegrin

Related books