Impairment of energy metabolism is a hallmark of brain aging and several neurodegenerative diseases, such as the Alzheimer’s disease (AD). Age- and disease-related hypometabolism is commonly associated with oxidative stress and they are both regarded as major contributors to the decline in synaptic plasticity and cognition. Neuroinflammatory changes, entailing microglial activation and elevated expression of inflammatory cytokines, also correlate with age-related cognitive decline. It is still under debate whether the mitochondrial dysfunction-induced metabolic deficits or the microglia activation-mediated neuroinflammation is the initiator of the cognitive changes in aging and AD. Nevertheless, multiple lines of evidence support the notion that mitochondrial dysfunction and chronic inflammation exacerbate each other, and these mechanistic diversities have cellular redox dysregulation as a common denominator. This research topic focuses on the role of a metabolic-inflammatory axis encompassing the bioenergetic activity, brain inflammatory responses and their redox regulation in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems are reviewed in terms of their causative or in-tandem occurrence and how the systemic environment, –e.g., insulin resistance, diabetes, and systemic inflammation–, impacts on brain function.

Impairment of energy metabolism is a hallmark of brain aging and several neurodegenerative diseases, such as the Alzheimer's disease (AD). Age- and disease-related hypometabolism is commonly associated with oxidative stress and they are both regarded as major contributors to the decline in synaptic plasticity and cognition. Neuroinflammatory changes, entailing microglial activation and elevated expression of inflammatory cytokines, also correlate with age-related cognitive decline. It is still under debate whether the mitochondrial dysfunction-induced metabolic deficits or the microglia activation-mediated neuroinflammation is the initiator of the cognitive changes in aging and AD. Nevertheless, multiple lines of evidence support the notion that mitochondrial dysfunction and chronic inflammation exacerbate each other, and these mechanistic diversities have cellular redox dysregulation as a common denominator. This research topic focuses on the role of a metabolic-inflammatory axis encompassing the bioenergetic activity, brain inflammatory responses and their redox regulation in healthy brain aging and neurodegenerative diseases. Dynamic interactions among these systems are reviewed in terms of their causative or in-tandem occurrence and how the systemic environment, -e.g., insulin resistance, diabetes, and systemic inflammation-, impacts on brain function.

Metabolic Drivers and Bioenergetic Components of Neurodegenerative Disease summarizes recent developments in intervention trials in neurodegenerative diseases, particularly Alzheimer's and Parkinson's, as well as increasing evidence for the overlap between drivers of metabolic and neurodegenerative disease that impact mitochondrial function and bioenergetics, and subsequently cellular function and pathophysiology. Topics covered include Brain Glucose and Ketone Utilization in Brain Ageing and Neurodegenerative Diseases; the Mitochondrial Hypothesis: Dysfunction, Bioenergetic Defects, and the Metabolic Link to Alzheimer's Disease; the Metabolic Impact on Neuroinflammation and Microglial Modulation in Neurodegenerative Diseases, the Impact of Circadian and Diurnal Rhythms on Cellular Metabolic Function and Neurodegenerative Diseases, and much more. - Summarizes the current status of and future research in Alzheimer's and Parkinson's diseases - Reviews the impact of the metabolic hypothesis on underlying mechanisms of neurodegenerative diseases

The brain is the most complex organ system in the human, both in the intricacy of its cellular architecture and in the extent of its repertoire of macromolecules. The Aging Brain presents the current state of understanding of molecular, cellular, and functional changes that occur in normal brain aging, and compares and contrasts those changes with events occurring in age-related neurodegenerative disorders. The chapters, written by world leaders in the field of brain aging, provide a timely and comprehensive consideration of key areas of this rapidly growing field of aging research. The topics covered include structural, functional, biochemical and molecular changes that occur during usual aging and in age-related neurological disorders. An emphasis is placed on emerging findings at the cellular and molecular levels. The roles of oxidative stress and perturbed energy metabolism in aging and neurodegenrative disorders are covered in considerable detail. In addition, the impact of aging and disease on specific neurotransmitter, neurotrophic factor and cytokine signaling pathways is reviewed. Finally, recent findings concerning possible approaches to reduce risk for age-related neurodegenerative disorders, such as caloric restriction, are presented. The collective body of information presented in The Aging Brain will provide those stepping into the field of brain aging with an overview of our current understanding of fundamental changes that occur in the aging brain, and their molecular and cellular underpinnings. At the same time, the book delves deeply into critical mechanistic details of brain aging that should prove valuable to experts in the field.

Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.* Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems

The editor of this volume, having research interests in the field of ROS production and the damage to cellular systems, has identified a number of enzymes showing ·OH scavenging activities details of which are anticipated to be published in the near future as confirmatory experiments are awaited. It is hoped that the information presented in this book on NDs will stimulate both expert and novice researchers in the field with excellent overviews of the current status of research and pointers to future research goals. Clinicians, nurses as well as families and caregivers should also benefit from the material presented in handling and treating their specialised cases. Also the insights gained should be valuable for further understanding of the diseases at molecular levels and should lead to development of new biomarkers, novel diagnostic tools and more effective therapeutic drugs to treat the clinical problems raised by these devastating diseases.

The book provides chapters on sex hormones and their modulation in neurodegenerative processes and pathologies, from basic molecular mechanisms, physiology, gender differences, to neuroprotection and clinical aspects for potential novel pharmacotherapy approaches. The book contains 14 chapters written by authors from various biomedical professions, from basic researchers in biology and physiology to medicine and veterinary medicine, pharmacologists, psychiatrist, etc. Chapters sum up the past and current knowledge on sex hormones, representing original new insights into their role in brain functioning, mental disorders and neurodegenerative diseases. The book is written for a broad range of audience, from biomedical students to highly profiled medical specialists and biomedical researchers, helping them to expand their knowledge on sex hormones in neurodegenerative processes and opening new questions for further investigation.

This book analyzes the effects of estrogens and progesterone on brain cells, the immune system, neuro inflammation, myelin formation and steroid receptor distribution, as well as their clinical impacts. It also explores the relationship between sex-steroid withdrawal and the development of brain symptoms such as hot flushes, sleep disorders, mood changes, depression and also cognitive disorders and dementia, as well as the effects of hormone menopause therapy on such symptoms and diseases. Starting with obstetrical history and cardiovascular risk in later life, the second part of the book examines the effects of estrogens and progestogens on vascular tissues, atherosclerosis and coronary heart diseases, as well as the impact of hormone replacement therapies on cardiovascular risks and mortality. This volume is a useful, clear and up-to-date tool for gynecologists, endocrinologists, neurologists and cardiologists, and serves as a valuable source of information for all physicians involved in women’s health.

Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.

While there are growing line of evidence for the role of the gut microbiome in different neurodegenerative diseases, the role and even the existence of the brain microbiome is only starting to be uncovered. Indeed, the brain was long considered to be a sterile environment and only recent studies have shown the presence of bacteria and fungi in the human central nervous system, and even inhabiting brain cells. The so called “brain microbiome” is appealing and immediately drew attention, since it is highly possible that microorganisms could have profound direct effects on a variety of processes in the brain, with the non-limiting examples of neurodegenerative and neurodevelopmental diseases triggering and progression. However, the brain microbiome remains poorly understood and even despite recent technological advances, is has only began to be explored.