TRP Channels as Therapeutic Targets

TRP Channels as Therapeutic Targets: From Basic Science to Clinical Use, Second Edition is a comprehensive reference on the roles of TRP Channels in health and disease states. Chapters are completely updated, withe new topics on TRP channels biology, the crystalline structure of TRP channels, targeting TRP channels for pain relief, the relationship with migraine, emerging pain targets, a comprehensive view of the role of TRP channels in respiratory diseases and COVID complications, anxiety relief, renal disease, arthritis, and therapeutic opportunities for thermal regulation. This is a great reference for broad segments of the scientific and medical community. Researchers working on TRP channel drug discovery will benefit from the overview of applications to conditions in specific organ systems. Clinicians interested in new drugs in the pipeline will also find this book helpful for biologic principles of action.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Chapter 1. Opening remarks: What makes TRP channels attractive therapeutic targets?
Introduction
Group I channels
Group II channels
THE physiological roles of TRP channels
Chapter 2. Biology of TRP channels
Introduction
Families of TRP channels
Physiological importance of TRP channels
TRP channels in the physiology of different cell systems
Cardiovascular system
Respiratory system
Endothelial barrier
Immune system
Pancreas
Reproductive system
Urinary system
Gastrointestinal tract, liver, and adipose tissue
Skeletal muscle and bone system
Central nervous system
Conclusion
Chapter 3. Targeting TRP channels: The emerging role of cryogenic electron microscopy in drug discovery
Introduction
Structure-based drug discovery
TRP channel structural biology
Cryo-electron microscopy
TRPV1
TRPV5
TRPV3
TRPM8
TRPA1
Future perspectives
Chapter 4. Thermo-TRPs: Temperature-sensitive TRP channels
Introduction
The definition of temperature sensitive channels
Discovery, functional characterization, and structural studies of thermo-TRPs
TRPV1
TRPV2
TRPV3
TRPV4
TRPA1
TRPM2
TRPM3
TRPM4/5
TRPM8
TRPC5
Basic thermodynamics of thermo-TRPs
Temperature sensor
Concluding remarks
Chapter 5. “TRP channelopathies”: TRP channel dysfunction in hereditary diseases
Overview
The mechanisms and the effects of TRP dysregulation in hereditary diseases
Hereditary diseases that are caused by TRP dysfunction
Perspectives
Chapter 6. Current understanding of TRP channels and their genomics: Implications in health research
Summary
TRP channels: General introduction
Classification and functions of TRP channels
Localization of TRP channels in cells and in subcellular organelles
TRP channels as regulators of development and gene expressions
Copy number variations of TRP channels
Alternate splicing of TRP genes
Cross talk between TRP channels and miRNA
Different variants of TRP channels
Pathogenic mutations of TRP channels (genetic mutations)
Penetration of TRP variants: No-phenotype to embryonic lethality
Nonconventional translation initiation of TRP channels
TRP variants as risk factors
Conclusion and future outlook
Chapter 7. TRP channel drug discovery strategies
Introduction
Overview of TRP channels
Drug discovery strategies
Conclusion
Chapter 8. High-dose capsaicin patch for pain relief: Clinical experience
Background
Efficacy of high-dose capsaicin in clinical practice: Clinical and observational trial data
Tolerability and adverse effects
Comparison with oral therapies
Cost and access
Practical considerations
Summary and conclusions
Chapter 9. Therapeutic uses of injectable capsaicin for pain
Introduction
Therapeutic uses of capsaicin
Potential mechanisms of analgesia
Conclusion
Chapter 10. Resiniferatoxin for permanent pain relief in cancer patients
Introduction: TRPV1 agonists and the treatment of pain
Periganglionic administration
Intrathecal administration
Epidural administration
Conclusions
Chapter 11. TRPV1 antagonists: Future drug discovery directions
Introduction
Clinical overview of TRPV1 antagonists
Issues to be addressed for clinical TRPV1 antagonists
Strategies for developing TRPV1 antagonists as drug candidates
Perspective
Chapter 12. TRPA1 antagonists for pain relief
Introduction
TRPA1 in thermal and chemical sensation
TRPA1 in mechanical nociception and primary hyperalgesia
TRPA1 in secondary (central) mechanical hyperalgesia
TRPA1 in pathophysiological pain models
Peripheral traumatic neuropathy
Peripheral diabetic neuropathy
Chemotherapy-induced neuropathy
Osteoarthritis
Sleep deprivation–induced pain hypersensitivity
Bacterial infection–induced pain and inflammation
Bladder pain syndrome
TRPA1 and human pain
TRPA1 antagonist hit finding and lead optimization
TRPA1 antagonists
TRPA1 antagonist phase 1 studies
TRPA1 antagonist phase 2 studies
TRPA1 antagonist phase 3 studies
TRPA1 agonists for pain relief?
Conclusions
Chapter 13. TRPM3: An emerging pain target (and more)
Introduction
TRPM3 basics II—Pharmacology
TRPM3 in the somatosensory system
Chapter 14. TRP channels and migraine
Migraine mediators
Neurogenic inflammation and CGRP
CGRP and migraine
TRP channels in PSNs
TRPV1 and migraine
TRPA1 and migraine
Other TRP channels and migraine
Conclusions
Chapter 15. TRP channels in the GU tract
Introduction
TRP channels in bladder afferents
TRP channels in nonneuronal cells in the urinary bladder
TRP role in bladder function
TRP role during micturition dysfunction
Interactions between different TRPs and between TRP and non-TRP receptors
TRP channels in the kidney, ureters, and urethra
TRP channels in the male genital tract
TRP channels in the female genital tract
TRP channels and cancer
Chapter 16. TRP channels in respiratory disorders
Introduction
Respiratory disorders
The role of TRP channels in respiratory disorders
Summary
Chapter 17. TRP channels: Emerging targets in COVID-19 and its complications
Introduction
SARS-CoV-2 and COVID-19
TRP channels
Inflammation and cytokine storm in COVID-19
Pain in COVID-19
Respiratory complications in COVID-19
Fever in COVID-19
Neurological complications in COVID-19
Cardiovascular complications in COVID-19
GI complications in COVID-19
Other complications in COVID-19
Post-COVID-19 (long-COVID-19) symptoms
TRP channels as emerging therapeutic targets
Abbreviations
Chapter 18. TRP channels in cardiovascular disease
Calcium signaling in the cardiovascular system
TRP channels and cardiovascular disease
TRP channels in cardiac hypertrophy
Role of TRP channels in cardiac hypertrophy signaling pathways
Pharmacological developments targeting TRP channels in cardiac hypertrophy
TRP channels and cardiac arrhythmias
TRPM4 and cardiac conduction disease
TRP channels and atrial fibrillation and fibrosis
TRP channels in pulmonary hypertension
Chapter 19. TRP channels in cerebral vascular disorders
Introduction
The cerebral circulation
TRP channels in cerebral vascular physiology
TRP channels in stroke
Alzheimer's disease and related dementias
Conclusion and perspectives
Chapter 20. TRPV1 in blood pressure regulation: A new therapeutic target in hypertension?
Historical background—General remarks
Structure and regulation of TRPV1
TRPV1-mediated vascular functions
Pharmacology of the vascular TRPV1
Physiological ligand and regulators of TRPV1 in the vasculature
Future perspectives
Chapter 21. Activating, inhibiting, and hijacking TRP channels for relief from itch
Introduction
Which sensory neurons signal itch?
Activating TRP channels to block itch
Inhibiting TRP channels to block itch
Hijacking TRP channels to deliver relief from itch
An unexpected role for TprV3: Mutations in TrpV3 result in itchy lesions found in Olmsted syndrome
Chapter 22. TRP channels in dermatology
Introduction
TRP channels in the skin
TRP channels in dermatological conditions
Concluding remarks: Therapeutic targeting, future directions
Chapter 23. Transient Receptor Potential (TRP) channels in cancer: Implications for drug discovery and development
Background and general aspects
The TRPC channel family
TRPC1
TRPC6
The TRPM channel family
TRPM1
TRPM2
TRPM4
TRPM7
TRPM8
The TRPV channel family
TRPV1
TRPA1
Summary
Chapter 24. TRP channel expression in the tumor microenvironment: Implications for tumor progression and metastasis
Cancer microenvironment; sensors of metabolic changes
Cancer-associated fibroblasts (CAFs) and TRP channels
Cancer-associated stellate cells and TRP channels
Angiogenesis and TRP channels
Tumor-infiltrating immune cells and TRP channels
TRP channels and macrophages
TRP channels and dendritic cells
T lymphocytes and TRP channels
Cancer infiltrating nerve fibers and TRP channels
Schwann cells, cancer microenvironment and TRP channels
Conclusions
Chapter 25. TRP channels as potential target molecules for pharmacotherapy of neurological diseases
Stroke
TRPM2
TRPM3
TRPM4
TRPM7
TRPM8
TRPV1
TRPV2
TRPV4
TRPC1
TRPC3
TRPC4
TRPC5
TRPC6
Migraine
TRPA1
TRPV1
TRPV4
TRPM8
TRPC4
Epilepsy
TRPA1
TRPC
TRPC1, TRPC4, 5
TRPC3, 6, 7
TRPV1
TRPV4
TRPM2
TRPM3
TRPM4, 6, 7
TRPM8
TRPP
Alzheimer's disease
TRPA1
TRPV
TRPC
TRPM
Parkinson's disease
TRPC1
TRPC3
TRPM2
TRPM7
TRPM8
TRPML1
TRPV1
Multiple sclerosis
TRPA1
TRPV1
TRPV6
TRPM2
TRPM8
TRPP1, 3
TRP channels and MS
Conclusions
Funding
Chapter 26. Targeting TRP channels for anxiety relief and improving mental health
The role of canonical TRP channels in building the brain and regulating its functions
Redox sensitive TRP channels in the brain
TRP channels in psychiatric disorders and mental retardation
The “addictive” TRP channels
Conclusions
Chapter 27. Potential of agents that modulate transient receptor potential (TRP) channels as therapies in arthritis
Introduction
Discovery of the TRPV1 channel
Discovery of capsaicin
The TRPV1 channel
Use of capsaicin analogs
The ultrapotent capsaicin agonist resiniferatoxin (RTX)
TRPV1 receptor antagonists
Discovery of the TRPA1 receptor and link to neurogenic inflammation
Other TRP ligands
Chapter 28. TRP channels as molecular targets to relieve endocrine-related diseases
Development and classification of TRP channels
TRP channels in the pancreas
TRP channels in the salivary gland
TRP channels in the adrenal gland
TRP channels in the mammary gland
TRP channels in the gallbladder
TRP channels in the sweat glands
TRP channels in the lacrimal gland
Conclusion and discussion
Abbreviations
Chapter 29. Transient receptor potential (TRP) channels in metabolic syndrome
Introduction
TRP channels
Functional characteristics of TRP channels in various aspects of MS and T2DM
Conclusion
Chapter 30. TRP channels in renal disease. Lessons from Polycystin-2 (TRPP2)
Transient receptor potential (TRP) superfamily
TRP channels and renal function
Lessons from Polycystin-2 in renal function and disease
TRP channels and Ca2+ oscillations in renal cells
Perspective
Chapter 31. TRP channels and thermoregulation; therapeutic opportunities
Introduction
Thermosensing by peripheral sensory neurons
Thermoregulation by thermal input to peripheral sensory neurons
Thermosensing at the hypothalamic thermoregulatory center
TRP channels regulate effector functions for thermoregulation
Body temperature change in mice with TRP channel KO
Perspectives
Chapter 32. Concluding remarks: Past, present, future
Background
A new dawn
TRP channels and sensory transduction
TRP channel structures
TRP channels and therapeutics
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

TRP Channels as Therapeutic Targets

Advances in Basic Science and Clinical Use

Purchase options

Institutional subscription on ScienceDirect

Arpad Szallasi