Preface

This book, *Acetylcholine – Recent Advances and New Perspectives*, comes more than 100 years after the discovery of acetylcholine as a neurotransmitter in 1921 by Otto Loewi. Since then, the study of this neurotransmitter has been a magnificent chronicle in terms of its chemistry, biochemistry, function in the central and peripheral nervous system, and its relevance for neurological disorders and diseases. To this day, the study of acetylcholine and its receptors astounds us with novel features and exciting news. This book focuses on the role of this neurotransmitter in the physiology of individual neurons as well as in neural circuits and specific brain regions. It illustrates acetylcholine in all its dimensions, from historical perspectives to technological advances, as well as the use of novel tools in health and disease, in various animal models and organisms related to this critical neurotransmitter. Targeted at students and researchers in biological, chemical, medical and history disciplines, this book provides an overview of the work that is being done on this key signaling molecule of the nervous system and brain and highlights any gaps and areas that would benefit from further exploration.

The book is organized into two sections. Section 1, "Acetylcholine, Receptors and Diseases", includes five chapters. Section 2 "Acetylcholine Esterase, Neurotoxin", includes two chapters.

Chapter 1, "Introductory Chapter: The Neurotransmitter Acetylcholine – A Young Centenarian" by Thomas Heinbockel, outlines the events leading to the discovery of acetylcholine as a neurotransmitter and the role that Otto Loewi and Henry Dale played in its discovery.

In Chapter 2, "Avian Muscarinic Receptors: An Update", Presannan Usha Aswathy, Suresh Narayanan Nair, Basavapura Mahadevappa Sanjay and Sanis Juliet take the reader to the world of birds. The authors review the distribution of avian muscarinic receptor subtypes, the characterization of muscarinic acetylcholine receptors in various organs and organ systems, and the sequence similarity of muscarinic acetylcholine receptor subtypes between various birds and animals.

Chapter 3, "Central Nicotinic and Muscarinic Receptors in Health and Disease" by Yousef Tizabi, Bruk Getachew, Vassiliy Tsytsarev, Antonei B. Csoka, Robert L. Copeland and Thomas Heinbockel, provides a detailed account of the interaction of nicotinic and muscarinic acetylcholine receptors. Following a brief description of acetylcholine actions and its central circuitry, the authors give an update on muscarinic and nicotinic acetylcholine receptors and how their interaction may impact neuropsychiatric and neurodegenerative diseases. Finally, the authors touch upon potential novel therapeutic interventions based on these interactions, particularly in relation to Alzheimer and Parkinson disease.

Chapter 4, "Modes of Acetylcholine Signaling in the Prefrontal Cortex: Implications for Cholinergic Dysfunction and Disorders" by Matthew Fecik and Lisa M. Savage, reviews the current views on the functional role of phasic versus tonic cholinergic signaling, the contributions of acetylcholine receptors, hydrolysis, and basal forebrain anatomy. The authors also examine the implications of these factors in acetylcholine signaling in terms of cholinergic circuit dysfunction that occurs in neurodegenerative diseases.

In Chapter 5, "Role of Acetylcholine in Chronic Diseases", Vandana Mohan, Dhirender Kaushik and Komal Arora provide a brief overview of acetylcholine, including its synthesis and degradation, the cholinergic system, and the influence of acetylcholine on different chronic diseases, including neurological complications, metabolic disorders, cardiac diseases, and immune disorders. The authors review the mechanistic approach of acetylcholine in different diseases and the therapies for recovering the levels of acetylcholine.

In Chapter 6, "Paraoxonase in Nervous System", Mohit Vijay Rojekar, Kaushalraj Sunil Dandegonker and Swati Ghanghurde address the paraoxonase (PON) family, which consists of three enzymes that are anti-oxidative. Any dysfunction in their action can play a role in the pathobiology of diseases that have a chronic inflammatory component. Relevant to this book, the PON family interacts with acetylcholine esterase (AChE), and PONs degrade the inhibitors of AChE, which can affect the prognosis of the treatment of Alzheimer disease by inhibitors of organophosphates.

In Chapter 7, "Neurotoxin Decontamination", Dongmei Ye and Susan Rempe discuss how nerve agents, a group of organophosphorus (OP) compounds, are potent neurotoxins used as chemical warfare agents and insecticides. OP nerve agents disrupt the CNS by inhibiting AChE function. The authors discuss strategies to counter OP agents using organophosphorus hydrolase (OPH), a bacterial enzyme that can detoxify a wide range of OP agents. In their studies, the authors optimized OPH by incorporating selected unnatural amino acids into OPH, with mutations targeting both active and allosteric binding sites.

I am grateful to IntechOpen for initiating this book project and for asking me to serve as its editor. Many thanks go to Maja Bozicevic at IntechOpen for guiding me through the publication process and for moving the book ahead in a timely fashion. Thanks are due to all contributors to this book for taking the time to first write their chapter proposals, compose their chapters, and make the requested revisions. Hopefully, all contributors will continue their research with many intellectual challenges and exciting new directions. I would like to thank my wife Dr. Vonnie D.C. Shields, associate dean and professor, Towson University, MD, USA, and our son Torben Heinbockel for the time that I was able to spend working on this book project during the past year. Finally, I am grateful to my parents Erich and Renate Heinbockel for their continuous support and interest in my work over many years.

**Thomas Heinbockel, Ph.D.**

**1**

Section 1

Acetylcholine, Receptors

and Diseases

Department of Anatomy, Howard University College of Medicine, Washington, DC, USA
