Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders

1st Edition - June 6, 2023

Editors: Heba Mohamed Mansour, Mahmoud Mohamed Khattab, Aiman El-Khatib

Paperback ISBN:

9 7 8 - 0 - 4 4 3 - 1 8 6 7 7 - 6

eBook ISBN:

9 7 8 - 0 - 4 4 3 - 1 8 6 7 8 - 3

Overexpression of receptor tyrosine kinases (RTKs) has been implicated in cancer. Increasing evidence suggests that dysregulation of RTKs is reported in many neurodegenerative and… Read more

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Overexpression of receptor tyrosine kinases (RTKs) has been implicated in cancer. Increasing evidence suggests that dysregulation of RTKs is reported in many neurodegenerative and psychiatric disorders.

Receptor Tyrosine Kinases in Neurodegenerative and Psychiatric Disorders provides a fundamental, pragmatic map of RTKs structure, activation, functions, mechanism of action, gene regulation, and signaling pathways in developing central nervous system (CNS), adult normal CNS, neurodegenerative and psychiatric disorders. Additionally, the structure, function, activation, and therapeutic potential of many growth factors have been covered. Here, international experts in the field offer a comprehensive discussion of results of pre-clinical and clinical studies of repositioning of anti-cancer receptor tyrosine kinase inhibitors (RTKIs) and other promising protein kinase inhibitors in various neurodegenerative disorders including, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis, and psychiatric disorders including, anxiety, depression, alcohol use disorder, and schizophrenia. In addition, the book discusses the obstacles and opportunities for the potential repositioning of kinase inhibitors in neurodegenerative and psychiatric disorders.

Cover image
Title page
Table of Contents
Copyright
Dedication
List of contributors
Preface
Acknowledgments
Section I. Receptor tyrosine kinase in the central nervous system in health and disease
Chapter 1. The molecular pathology of neurodegenerative and psychiatric disorders
1. Introduction
2. Alzheimer's disease
3. Parkinson's disease
4. Multiple sclerosis
5. Psychiatric disorders
Chapter 2. Receptor tyrosine kinases: an overview
1. Introduction
2. Receptor tyrosine kinases families and subfamilies
3. Receptor tyrosine kinase signaling
4. Biological expression and functions in the brain and other tissues
5. Roles of RTKs in several diseases
6. Molecular mechanisms of receptor tyrosine kinase-mediated neurodegeneration
7. RTKs involved in neurodegeneration
8. Current status of receptor tyrosine kinases inhibitors as therapeutic targets
9. Conclusion
Chapter 3. Roles of Trk receptors, tyrosine kinase receptors for neurotrophins, in the developing CNS
1. Introduction
2. Intracellular signaling via Trk tyrosine kinase receptors
3. Role of brain-derived neurotrophic factors/tropomyosin receptor kinase B (BDNF/TrkB) system in synaptic function
4. Synaptic proteins and neurotrophins/receptors system
5. Role of tropomyosin receptor kinase (TrkR) and P75 neurotrophin receptors (p75NTR) in neurogenesis
6. Aging and neurotrophins receptors
7. Neurotrophins/receptors signaling in Alzheimer's disease
8. Conclusions
Chapter 4. Receptor tyrosine kinases (RTKs): from biology to pathophysiology
1. Introduction
2. Structure of receptor tyrosine kinases (RTKs)
3. Classification of RTKs
4. Receptor tyrosine kinases (RTKs) in CNS
5. Expression and activation of RTK in neurodegenerative disorders
6. Expression and activation of RTKs in psychiatric disorders
7. Concluding remarks
Chapter 5. Growth factors and their receptors: multitasking functionality in health and disease
1. Introduction
2. Neurodegenerative diseases
3. Role of receptor tyrosine kinase (RTK) in cell signaling
4. Major classes of growth factors acting in the nervous system
5. Growth factor as therapeutic strategies in neurodegenerative disorders: future directions
6. Summary and conclusion
Chapter 6. Regulation of receptor tyrosine kinase gene expression
1. Introduction
2. Receptor tyrosine kinase genes
3. Regulation of receptor tyrosine kinase gene expression
4. Mechanism of receptor tyrosine kinase activation
5. Regulation of receptor tyrosine kinase activity
6. Downstream effectors of RTKs regulating the pathophysiology of neurodegenerative diseases and psychiatric disorders
7. Concluding remarks and future perspectives
Section II. Role of receptors tyrosine kinases (RTKs) in neurodegenerative and psychiatric disorders
Chapter 7. Role of receptor tyrosine kinases in neurodegenerative disorders
1. Introduction
2. Role of RTK in neurodegenerative and psychiatric disorders
3. Role of receptor tyrosine kinase in Parkinson's disease
4. Role of RTKs in amyotrophic lateral sclerosis
5. Role of RTKs in multiple sclerosis
6. Conclusion
Chapter 8. Insights into receptor tyrosine kinases signaling in neurodegenerative disorders: opportunities and translational perspectives
1. Introduction
2. Rearranged during transfection receptors
3. Epidermal growth factor receptor (EGFR; HER; or ErbB)
4. Vascular endothelial growth factor receptors
5. Tyro3, Axl, and Mertk (TAM receptors)
6. Tropomyosin receptor kinase receptors
7. Summary and conclusion
Chapter 9. Receptor tyrosine kinases in major depressive disorder
1. Introduction
2. Dysregulation of neuregulin-1/ErbB pathway in MDD
3. Conclusion
Section III. Therapeutic potential of RTK modulators in neurodegenerative and psychiatric disorders
Chapter 10. Repositioning of receptor tyrosine kinase inhibitors: from cancer to neurodegenerative and psychiatric disorders
1. Introduction
2. Neurodegenerative disorders
3. Psychiatric disorders
4. Summary
5. Conclusion
Chapter 11. Protein kinase inhibitors as therapeutics in neurodegenerative and psychiatric disorders: progress, challenges, and recommendations
1. Introduction
2. The clinical experience
3. Multispecific inhibitors
4. Toward oligospecific inhibitors
5. Toward dual/monospecific inhibitors
6. Concluding remarks
Index

Heba Mohamed Mansour

Heba M. Mansour works at Central Administration of Biologicals, Innovative Products, and Clinical Studies (Bio-Inn), Egyptian Drug Authority (EDA). Heba is also pursuing her Ph.D. in pharmacology and toxicology at Faculty of Pharmacy, Cairo University. Her research interests lie in the potential repositioning of anti-cancer drugs especially kinase inhibitors in neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. She has authored several articles, including research papers in prestigious international journals, book chapters, and review articles.

Affiliations and expertise

Central Administration of Biological, Innovative Products, and Clinical Studies (Bio-INN), Egyptian Drug Authority (EDA), Egypt.

Mahmoud Mohamed Khattab

Prof. Dr. Mahmoud M. Khattab is emeritus professor of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University (FOPCU). Between 10-1994 to 12-1996, he was a Ph.D. Fellow in Nephrology Laboratory, at College of Medicine, Munster University, Munster, Germany. He worked as University Staff in Faculty of Pharmacy (2000-2006), and Faculty of Medicine (2008-2010), King Saud University, Riyadh, KSA. He joined German University in Cairo between 2006-2008. He worked as part-time staff in many Universities including Beni Suef University, 6 October University, and Ahram Canadian University. He has contributed to two postgraduate Diplomas at FOPCU, namely the Pharmacovigilance Diploma and IT-Based Clinical Toxicology Diploma. His current research interest includes RAS-based, and Tyrosine Kinase-based targeting therapies in neurodegenerative and musculoskeletal diseases. Management of chemotherapy-induced diseases including depression and neuropathy by repurposing of known pharmacological mechanisms is another area of interest. Furthermore, he has current research projects in Breast Cancer therapeutic-enhancing modalities, including nutritional one. Furthermore, He is a consultant member in many scientific committees at the Egyptian Drug Authority (EDA), including Pharmacovigilance, Cosmetic Products, Neuropsychiatry, Internal Medicine committees.

Affiliations and expertise

Professor of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt

Aiman El-Khatib

Prof. Dr. Aiman Saad El-Khatib is currently the Vice President of the Egyptian Drug Authority. He is a Professor of Pharmacology and Toxicology in the Faculty of Pharmacy, Cairo University since May 2002. He held several leadership positions in Cairo University including Vice President for Graduate Studies and Research Affairs, Dean of Faculty of Pharmacy, Vice Dean for Education and Students Affairs as well as Vice Dean for Community Service and Environment Development. Additionally, he held the post of Assistant Minister of Health and Population for Pharmaceutical Affairs. His primary research area of interest is investigation of the pharmacological properties of various drugs, including natural products on the gastrointestinal tract, cardiovascular and central nervous systems. He published numerous articles in international journals. His awards include Cairo University Scientific Research Fosterage in field of Theoretical and Applied Biological Sciences in 2004, Silver and Gold Medal of Merit from Egyptian Syndicate of Pharmacists in 2004 and 2005.

Affiliations and expertise

Vice President, Egyptian Drug Authority (EDA) and Professor of Pharmacology and Toxicology, Cairo University, Cairo, Egypt