In the past several years, there has been an exciting body of new research that links impairments in the expression or function of neuronal chloride transporters to a growing number of diseases spanning from autism to brain aging. This book introduces the core concepts and recent advances in understanding the physiology and pathophysiology of neuronal chloride transporters, with particular focus on the KCC and NKCC families of proteins. Chloride transporter biology is reviewed, including roles in setting the transmembrane chloride gradient and in their chloride transport-independent functions, such as regulating excitatory neurotransmission. Chapters are also dedicated to addressing post-translational modifications and trafficking of chloride transporters, protein interaction partners, and genetic and environmental factors that regulate expression in neurons, and novel therapies to treat neurological disease. This new volume will provide readers with an up-to-date summary of the recent advances in neuronal chloride transporter research, with particular emphasis on some of the key emerging topics in the field. Summarizes role of NKCC and KCC in regulating inhibitory and excitatory neurotransmissionReviews the molecular and cellular biology of neuronal chloride transportersLinks chloride transporter deficiencies to autism, epilepsy, schizophrenia, and moreIdentifies the role of transporter deficiencies in pain and brain and spinal cord injuryDiscusses drug research targeting on neuronal chloride transporters for nervous system diseases INDICE: Part I: Function of neuronal chloride transporters in regulating neuronal chloride homeostasis 1. Methods for investigating neuronal chloride regulation 2. The relationship between neuronal chloride regulation, GABAergic inhibition, and neuronal excitability: 3. How Chloride transporter activities shape early brain development 4. The function of chloride transporters in regulating cell migration and cortical development Part II: Function of KCC2 in regulating excitatory synapse development 5. KCC2 regulates dendritic spine development 6. KCC2 regulates AMPA receptor trafficking and the function of excitatory synapses 7. KCC2 is a hub protein in balancing excitation and inhibition Part III: The molecular and cellular biology of neuronal chloride transporters 8. Structures of KCC and NKCC family of chloride transporters in relationship to their functions 9. Developmental timeline of neuronal chloride transporter expression in different brain regions and sensory organs in various animal species 10. Post-translational modification of chloride transporters: oligomerization, calpain cleavage and degradation 11. Regulation of the chloride transportation rate by glycosylation, phosphorylation, and intracellular trafficking of neuronal chloride transporters 12. Proteins that interact with neuronal chloride transporters 13. Genetic and environmental regulators of chloride transporter gene expression Part IV: The involvement of neuronal chloride transporter deficiencies in nervous system diseases 14. The involvement of neuronal chloride transporter dificiencies in epilepsy 16. KCC2 reduction following brain injury 17. Reduction in KCC2 expression and function as a result of brain ischemia and excitotoxicity 18. Disruptions in Chloride transporters as a common cause of autism spectrum disorders 19. Chloride transporter in early brain development and Down syndrome 20. Microglial modulation of KCC2 in neuropathic pain and spinal cord injury 21. Astroglial regulation of neuronal chloride homeostasis 22. The relationship between neuronal chloride transporters, brain aging, and neurodegenerative diseases Part V: Drug discovery targeting neuronal chloride transporters 23. Utilization of NKCC1 blockers as drugs to treat brain disorders 24. The development of pharmaceutical regulators of KCC2
- ISBN: 978-0-12-815318-5
- Editorial: Academic Press
- Encuadernacion: Rústica
- Páginas: 650
- Fecha Publicación: 01/06/2020
- Nº Volúmenes: 1
- Idioma: Inglés