Humana Oxidative Neural Injury (Contemporary Clinical Neuroscience)

Twenty-five years ago, Earl R. Stadtman, PhD discovered that specific enzymes regulating metabolism can be inactivated by oxidation [1]. He later showed that age-related oxidative modification contributes, at least in part, to age-related loss of function of the enzymes [2, 3]. Dr. Stadtman broke the ground for a new field of study to discover how oxidative stress contributes in significant ways to age-related cellular dysfunction and protein accumulation and that oxidation in the aging brain influences Alzheimer’s disease, ischemia-reperfusion injury, amyotrophic lateral sclerosis, and lifespan [4–6]. Today, his research and mentorship have positively influenced the work of hundreds of scientists in this field. We dedicate this book to Dr. Earl R. Stadtman (1912–2008), in celebration of his passion for science and his superior collaborative and mentorship skills. This book is comprised of three sections. The first describes the valuable roles reactive oxygen species (ROS) and reactive nitrogen species (RNS) play in cellular biology. The second section provides an overview of redox imbalance injury with effects on mitochondria, signaling, endoplasmic reticular function, and on aging in general. The third section takes these mechanisms to neurodegenerative disorders and provides a state-of-the-art look at the roles redox imbalances play in age-related susceptibility to disease and in the disease processes. In the first section we attempt to answer a question posed by Dr. Stadtman, ‘‘Why have cells selected reactive oxygen species to regulate cell signaling events’’ [7]. Review From the reviews: “This book addresses how oxidative stress contributes to age-related cellular dysfunction particularly in Alzheimer's ischemia, Parkinson's disease, and other neurodegenerative conditions. The book fills a niche, addressing the current molecular understanding of oxidative stress and its role in pathophysiology. … it is most appropriate for the many neuroscientists around the world contemplating how to identify the next best approach for targeted therapy for several neurodegenerative diseases. … the book is a good resource for libraries with PhD graduate students and molecular neuroscience laboratories.” (Joseph I. Sirven, Doody’s Review Service, December, 2009) From the Back Cover Edited bySigrid Veasey, M.D.Center for Sleep and Respiratory NeurobiologyDepartment of MedicineUniversity of Pennsylvania Oxidative changes are observed in healthy aging of the nervous system, neurodegenerative processes and other forms of neural injury. At the same time, reactive oxygen species and reactive nitrogen species play critical roles in rapid response signaling, in learning, plasticity and in neuronal homeostasis. How do reactive oxygen and nitrogen molecules play such divergent roles in physiology and pathophysiology? How do these molecules contribute to neural injury, dysfunction and loss? The text Oxidative Neural Injury brings together international experts to systematically describe the biochemistry of reactive oxygen and nitrogen species signaling and then integrate this biochemistry into the neurobiology of redox in learning and plasticity and in healthy aging. This information will serve as the much-needed infrastructure for understanding in a more comprehensive manner how redox modifications contribute to neurodegenerative processes, in both early and late injury. Indeed, it is apparent that the development of effective therapies for neurodegenerative processes will first require a careful understanding of these critical roles of reactive oxygen and nitrogen molecules in neuronal signaling and cellular homeostasis, and this must be complemented with a comprehensive understanding of how reactive oxygen and nitrogen species perturb specific organelle and cellular functions.