From Oxidative Stress to Cognitive Decline - Towards Novel Therapeutic Approaches

From Oxidative Stress to Cognitive Decline - Towards Novel Therapeutic Approaches

Author: Touqeer Ahmed

Publisher: Frontiers Media SA

Published: 2023-09-01

Total Pages: 193

ISBN-13: 2832534104

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Oxidative stress plays multiple roles in the pathobiology of several neurodegenerative disorders and Alzheimer’s disease in particular. Increased oxidative stress in the brain is suggested to be associated with aging, greater amounts of easily oxidizable unsaturated fatty acids, higher utilization of oxygen by the brain, mitochondrial-derived free radicals, calcium homeostasis, and glutamate-induced excitotoxicity. Moreover, environmental chemicals/toxins, heavy metals, and an imbalanced diet might increase oxidative stress potentially leading to a decrease in cognitive functions. Cellular health is also dependent on the levels of nicotinamide adenine dinucleotide (NAD+). It has been well documented that NAD+ is an important coenzyme for over 400 different oxidoreductases and turns out to be a relevant factor to the oxidative stress in the brain. Since the last two decades, NAD+ has been shown to be more than a mere regulator of metabolism, but rather may play a key role in the aging process. NAD+ along with sirtuins are important for various neurophysiological functions, and depletion of NAD+ may be associated with compromised physiological and cognitive functions. To protect the brain from oxidative stress, a modest endogenous protective system works in the brain through dedicated enzymatic machinery. Key enzymes are superoxide dismutase and catalase, which provide protection against oxidative stress. Aging, various neurological disorders, and chronic inflammation might also affect the levels of these protective enzymes and reduce their levels. Natural compounds, including polyphenols, can offer protection through NAD+ and various other mechanisms. Based on these factors it is becoming more and more clear that oxidative stress and its devastating effects on cognitive decline represents a major health issue in neurobiology. There is a need to identify potential compounds and therapeutic targets for mitigating oxidative stress and/or to strengthen the protective endogenous mechanisms. Novel approaches aiming to support and provide protective mechanisms in the brain will represent a great success in therapeutics. We welcome all article types focusing on the analysis and investigation of oxidative stress - originated from different sources - and its impairing effects on the brain. We will also accept studies investigating naturally occurring compounds, standard medications, and nutraceuticals that have an impact on oxidative stress, NAD+ metabolism and medical and health applications. For this, the aim of this Research Topic is to provide novel insights on oxidative stress (induced by any mechanism) impact on brain health, and on the strengthening of brain-protective mechanisms, supporting cognitive functions.


Brain Aging

Brain Aging

Author: David R. Riddle

Publisher: CRC Press

Published: 2007-04-19

Total Pages: 408

ISBN-13: 9781420005523

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Recognition that aging is not the accumulation of disease, but rather comprises fundamental biological processes that are amenable to experimental study, is the basis for the recent growth of experimental biogerontology. As increasingly sophisticated studies provide greater understanding of what occurs in the aging brain and how these changes occur


Oxidative Neural Injury

Oxidative Neural Injury

Author: Sigrid C. Veasey

Publisher: Springer Science & Business Media

Published: 2009-05-28

Total Pages: 224

ISBN-13: 1603273425

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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].


Handbook of Intervention and Alzheimer’s Disease

Handbook of Intervention and Alzheimer’s Disease

Author: C.A. Raji

Publisher: IOS Press

Published: 2024-02-22

Total Pages: 768

ISBN-13: 1643685015

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It is almost 120 years since Alzheimer’s disease (AD) was first reported, and the concept of managing some of the modifiable risk factors associated with the disease has been present from the outset. Intervening to manage risk factors as a way of tackling AD is not new, but optimizing brain health as a way of minimizing risk and maximizing the potential benefits of revolutionary new treatments for AD is becoming increasingly important. This book, the Handbook of Intervention and Alzheimer’s Disease, presents 47 papers exploring factors which may either inspire or inform future treatment and clinical trials. While novel interventions such as anti-amyloid immunotherapy present great opportunities, they may also increase the risk of brain bleeds and edema, which in turn may lead to adverse clinical outcomes. Such adverse outcomes are demonstrably more likely to occur in persons with poor brain health, so improved management of the risk factors which make up the AD preventome will also minimize the risks associated with such novel therapies. The papers in this volume can therefore be thought of as offering insight into those factors that can optimize brain health or providing key insights into interventions which may achieve such outcomes. Together with its companion volume on prevention, the book provides a comprehensive overview of strategies for tackling Alzheimer’s disease, and will be of interest to all those working in the field. Cover illustration: Improved hypoperfusion (resolving blue colors) on ASL MRI Z-score maps superimposed on structural MRI scans at baseline and one year in a PET amyloid-positive research participant with cognitive complaints undergoing one year of multi-domain personalized brain health interventions (vascular disease management, dietary optimization, sustained physical activity etc.). Permission to use this figure was granted both by the study P.I. Dr. David Merrill, MD, PhD, of the Pacific Neuroscience Institute and the research participant.


Neuropsychiatric Disorders

Neuropsychiatric Disorders

Author: Manfred Gerlach

Publisher: Springer Science & Business Media

Published: 2007-12-28

Total Pages: 326

ISBN-13: 3211735747

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This multidisciplinary book includes current research papers and reviews in the areas of basic neuroscience, neural mechanisms underlying neurodegenerative disorders. It further includes new approaches for neuroprotective treatments, clinical, neurobiological and treatment aspects of psychiatric disorders. The book was conceived as a celebration of the professional life and work of Peter Riederer to mark the occasion of his retirement.


Oxidative Stress and Neurodegenerative Disorders

Oxidative Stress and Neurodegenerative Disorders

Author: G. Ali Qureshi

Publisher: Elsevier

Published: 2007-03-22

Total Pages: 795

ISBN-13: 0080489494

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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


Alzheimer's Disease

Alzheimer's Disease

Author: Inga Zerr

Publisher: BoD – Books on Demand

Published: 2015-07-01

Total Pages: 374

ISBN-13: 9535121375

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There is a wide scope of clinical phenomenology in Alzheimers disease, regarding the age of onset, presenting features, rate of progression and appearance of other clinical manifestation. Although clinical appearance and neuropathological hallmarks have been defining AD since its first description, major factors which trigger pathology are still unknown. The role of comorbidity is discussed controversially. Important environmental risk factors in AD development are continuous stress, low education and cardiovascular risk factors such as alcohol intake, smoking, hypertension. The role of lipids and cholesterol has been recognized, but the relevant pathogenetic steps are still to be identified. There is an urgent need to understand molecular disease pathogenesis in order to develop early therapeutic targets for the disease.


Redox Proteomics

Redox Proteomics

Author: Isabella Dalle-Donne

Publisher: John Wiley & Sons

Published: 2006-08-11

Total Pages: 978

ISBN-13: 0471973114

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Methodology and applications of redox proteomics The relatively new and rapidly changing field of redox proteomics has the potential to revolutionize how we diagnose disease, assess risks, determine prognoses, and target therapeutic strategies for people with inflammatory and aging-associated diseases. This collection brings together, in one comprehensive volume, a broad array of information and insights into normal and altered physiology, molecular mechanisms of disease states, and new applications of the rapidly evolving techniques of proteomics. Written by some of the finest investigators in this area, Redox Proteomics: From Protein Modifications to Cellular Dysfunction and Diseases examines the key topics of redox proteomics and redox control of cellular function, including: * The role of oxidized proteins in various disorders * Pioneering studies on the development of redox proteomics * Analytical methodologies for identification and structural characterization of proteins affected by oxidative/nitrosative modifications * The response and regulation of protein oxidation in different cell types * The pathological implications of protein oxidation for conditions, including asthma, cardiovascular disease, diabetes, preeclampsia, and Alzheimer's disease Distinguished by its in-depth discussions, balanced methodological approach, and emphasis on medical applications and diagnosis development, Redox Proteomics is a rich resource for all professionals with an interest in proteomics, cellular physiology and its alterations in disease states, and related fields.


Protein Carbonylation

Protein Carbonylation

Author: Joaquim Ros

Publisher: John Wiley & Sons

Published: 2017-06-26

Total Pages: 416

ISBN-13: 1119074916

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Protein carbonylation has attracted the interest of a great number of laboratories since the pioneering studies at the Earl Stadtman’s lab at NIH started in early 1980s. Since then, detecting protein carbonyls in oxidative stress situations became a highly efficient tool to uncover biomarkers of oxidative damage in normal and altered cell physiology. In this book, research groups from several areas of interest have contributed to update the knowledge regarding detection, analyses and identification of carbonylated proteins and the sites where these modifications occur. The scientific community will benefit from these reviews since they deal with specific, detailed technical approaches to study formation and detection of protein carbonyls. Moreover, the biological impact of such modifications in metabolic, physiologic and structural functions and, how these alterations can help understanding the downstream effects on cell function are discussed. Oxidative stress occurs in all living organisms and affects proteins and other macromolecules: Protein carbonylation is a measure of oxidative stress in biological systems Mass spectrometry, fluorescent labelling, antibody based detection, biotinylated protein selection and other methods for detecting protein carbonyls and modification sites in proteins are described Aging, neurodegenerative diseases, obstructive pulmonary diseases, malaria, cigarette smoke, adipose tissue and its relationship with protein carbonylation Direct oxidation, glycoxidation and modifications by lipid peroxidation products as protein carbonylation pathways Emerging methods for characterizing carbonylated protein networks and affected metabolic pathways