Oxidative Stress: How has it been Considered in the Design of New Drug Candidates for Neurodegenerative Diseases? PDF Download

Author: Claudio Viegas Jr
Publisher: Frontiers Media SA
ISBN: 2889664171
Category : Science
Languages : en
Pages : 86

View

Book Description

Author: G. Ali Qureshi
Publisher: Elsevier
ISBN: 0080489494
Category : Science
Languages : en
Pages : 795

View

Book Description
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

Author: Ismail Laher
Publisher: Springer
ISBN: 9783642300172
Category : Medical
Languages : en
Pages : 0

View

Book Description
The focus of this collection of illustrated reviews is to discuss the systems biology of free radicals and anti-oxidants. Free radical induced cellular damage in a variety of tissues and organs is reviewed, with detailed discussion of molecular and cellular mechanisms. The collection is aimed at those new to the field, as well as clinicians and scientists with long standing interests in free radical biology. A feature of this collection is that the material also brings insights into various diseases where free radicals are thought to play a role. There is extensive discussion of the success and limitations of the use of antioxidants in several clinical settings.

Author: Andreia Neves Carvalho
Publisher: Frontiers Media SA
ISBN: 2832523536
Category : Science
Languages : en
Pages : 152

View

Book Description
Redox homeostasis results from the balance between the production of reactive species (e.g. ROS, RNS, etc) and their detoxification by endogenous or exogenous antioxidants. ROS play several important physiological roles, however, their excessive production or impaired detoxification is associated with oxidative stress and cellular injury. Importantly, oxidative damage to vulnerable central nervous system (CNS) cells is a common pathological feature of several neurodegenerative diseases. Antioxidants have been considered as attractive potential therapeutic agents to prevent or halt disease progression but the clinical efficacy of antioxidant treatment strategies is still marginal. Improvement of antioxidant therapy effectiveness might involve adjustment of preclinical to clinical settings and development of new efficient delivery methods and will require a more in-depth knowledge of cellular redox-signaling mechanisms. Promising novel redox-based therapeutic strategies are gaining relevance to combat oxidative stress associated with neurodegenerative diseases. These include boosting the endogenous antioxidant machinery through activation of the antioxidant master regulator Nrf2 (nuclear factor erythroid 2-related factor 2) or modulation of ROS production by NOX (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase) inhibitors. Redox regulation of key cellular functions is currently recognized as an important cellular signaling mechanism and events such as post-translational modifications (e.g. S_glutathionylation, S_nitrosylation, glycosylation, etc) play important roles in redox signal transduction and might be instrumental to uncover pathological mechanisms and identify novel therapeutic targets in neurodegenerative diseases. This Research Topic focuses on redox signaling mechanisms and aims to provide novel insights into the role of redox-signaling, with particular emphasis on redox regulation involving post-translational modifications, in the pathophysiology of neurodegenerative diseases. Moreover, it aims to present an overview of the potential of antioxidants as therapeutics for CNS disorders with a special focus on emerging novel therapeutic redox-based strategies. We are particularly interested in studies: -addressing new redox-based molecular mechanisms contributing to neurodegenerative diseases; -exploring the role of naturally occurring compounds, standard medications, and nutraceuticals with antioxidant properties in modulating redox-signaling pathways and limiting and/or preventing oxidative damage associated with these disorders; -addressing mechanistically the role of post-translational modifications in the pathophysiology of neurodegenerative disorders.

Author: Shamim I. Ahmad
Publisher: Springer Science & Business Media
ISBN: 1461406536
Category : Medical
Languages : en
Pages : 421

View

Book Description
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.

Author: Yuan Luo
Publisher: CRC Press
ISBN: 1420026550
Category : Medical
Languages : en
Pages : 524

View

Book Description
Oxidative Stress and Age-Related Neurodegeneration brings together researchers from a variety of fields to compare normal aging and disease-related neurodegeneration in terms of susceptibility to and effects of oxidative stress. They address how these effects can be attenuated, and examine whether antioxidants and natural micronutrients, such as those found in Gingko biloba, green tea, blueberries, and grape seed extract, can play a role. The book includes various ways research is getting to the core of neurodegenerative disease, including the use of proteomics, comparisons to related diseases, and examinations at the cellular and molecular levels.

Author: Touqeer Ahmed
Publisher: Frontiers Media SA
ISBN: 2832534104
Category : Science
Languages : en
Pages : 193

View

Book Description
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.

Author: Girish Kumar Gupta
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 311036882X
Category : Science
Languages : en
Pages : 297

View

Book Description
Chemical Drug Design provides a compact overview on recent advances in this rapidly developing field. With contributions on in silico drug design, natural product based compounds, as well as on ligand- and structure-based approaches, the authors present innovative methods and techniques for identifying and synthetically designing novel drugs.

Author: Daniela Schuster
Publisher: Frontiers Media SA
ISBN: 2889633594
Category :
Languages : en
Pages : 336

View

Book Description
In the current drug research environment in academia and industry, cheminformatics and virtual screening methods are well established and integrated tools. Computational tools are used to predict a compound’s 3D structure, the 3D structure and function of a pharmacological target, ligand-target interactions, binding energies, and other factors essential for a successful drug. This includes molecular properties such as solubility, logP value, susceptibility to metabolism, cell permeation, blood brain barrier permeation, interaction with drug transporters and potential off-target effects. Given that approximately 40 million unique compounds are readily available for purchase, such computational modeling and filtering tools are essential to support the drug discovery and development process. The aim of all these calculations is to focus experimental efforts on the most promising candidates and exclude problematic compounds early in the project. In this Research Topic on virtual activity predictions, we cover several aspects of this research area such as historical perspectives, data sources, ligand treatment, virtual screening methods, hit list handling and filtering.

Author: Sigrid C. Veasey
Publisher: Humana Press
ISBN: 9781603273411
Category : Medical
Languages : en
Pages : 218

View

Book Description
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].