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

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

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

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

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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: Sigrid C. Veasey
Publisher: Springer Science & Business Media
ISBN: 1603273425
Category : Medical
Languages : en
Pages : 224

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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].

Author: Paolo Zatta
Publisher: World Scientific
ISBN: 9789812796691
Category : Medical
Languages : en
Pages : 546

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Book Description
Numerous studies have established a clear connection between neuronal oxidative stress and several neurodegenerative diseases, with consequential damages to lipids, proteins, nucleic acids, etc. In addition, several modifications indicative of oxidative stress have been described in association with neurons, neurofibrillary tangles and senile plaques in Alzheimer''s disease, including advanced glycation end products and free carbonyl oxidation. Oxidative damage and antioxidant responses are now well characterized, but sources of damaging free radicals are yet to be fully understood. Evidences of alteration in metal ions metabolism have been reported in various diseases like Alzheimer''s, Wilson, Menkes, Prion, Pick, Huntington disease, epilepsy and other pathological events. Thus, metal ions play a pivotal role in neurodegenerative phenomena. Chelation therapy is still in the early days of its development, but research in this area could lead to new products that could revolutionize treatment. Two international conferences on OC Metals and the Brain: From Neurochemistry to NeurodegenerationOCO (Padova, Italy, 2000 and Fez, Morocco, 2002) were recently held to discuss the role of metal ions in neurophysiopathology. A third will be held in 2005 in Johannesburg, South Africa. This book follows the same train of thought as those conferences, in order to highlight the unquestionable importance of metal ions in the research on the neurophysiopathology of neurodegenerative diseases. The excellent reputation of the scientists who have contributed to this project ensures the quality of the chapters presented here, and hopefully this will help spur new research initiatives in the field, which is still in its infancy. Contents: Metal-Catalyzed Redox Activity in Neurodegenerative Disease (M A Taddeo et al.); Aluminum and Central Nervous System Morphology in Hemodialysis (E Reusche); Transition Metals, Oxidation, Lipoproteins, and Amyloid-: Major Players in Alzheimer''s Disease (A Kontush); Molecular Basis of Copper Transport: Cellular and Physiological Functions of Menkes and Wilson Disease Proteins (ATP7A and ATP7B) (D R Kramer et al.); Copper-Zinc Superoxide Dismutase and Familial Amyotrophic Lateral Sclerosis (M B Yim et al.); Copper and Prion Disease (J Sasson & D Brown); Metallothioneins in Neurodegeneration (M Aschner et al.); Iron and Neurodegeneration (S L Grab & J R Connor); Iron, Neuromelanin, and -Synuclein in Neuropathogenesis of Parkinson''s Disease (K L Double et al.); Iron and Epilepsy (W-Y Ong et al.); Role of Iron Metabolism in Multiple Sclerosis (M J Kotze et al.); Neuroprotective Effects of Lithium (S Ermidiou-Pollet & S Pollet); and other articles. Readership: Academics, graduate students and researchers in neurology, psychiatry, neuroscience and environmental health."

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

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

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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: Cho-Tsun Or
Publisher: Open Dissertation Press
ISBN: 9781361005170
Category : Medical
Languages : en
Pages : 174

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Book Description
This dissertation, "Pharmacological Effects of Medicinal Herbs on Oxidative Stress Related Neurodegenerative Diseases" by Cho-tsun, Or, 柯楚浚, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Neurodegenerative diseases are characterized by progressive loss and altered functions of neurons. They include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Although there are approved drugs to treat neurodegenerative diseases, most of them only provide symptomatic improvement and have little or no impact on disease progression. Recent findings show that oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases. It could cause apoptosis of neurons. Therefore, rescuing neuronal cell death from oxidative stress challenges could be one of the important therapeutic strategies. Moreover, neural regeneration by neural stem cells is believed to be a potential method for functional recovery after neural damage. The first essential step of neural stem cell therapy is to allow the neural stem cells to survive and grow. Therefore, another aspect of treating neurodegenerative diseases is to search for agents which enhance proliferation of neural stem cells. Herbal medicine is increasingly being used in recent decades to enhance general health and well-being. In this project, three medicinal herbs including Ligusticum chuanxiong (LCX), Ganoderma lucidum (LCZ) and Cimicifuga racemosa (BC) were studied. In the first part of the study, the neuroprotective effects of the three medicinal herbs were tested. Among them, BC and LCX extracts were found to rescue PC12 cells from neuronal cell death induced by hydrogen peroxide (H2O2), as measured by MTT assays. Cim A and Z-lig, bioactive compounds of BC and LCX, respectively, also exerted the neuroprotective effects on PC12 and neuro-2a cells. Both compounds rescued the neuronal cell death via inhibition of apoptosis as measured by caspase-3 activity assays. As for the mechanisms involved, Cim A and Z-lig were found to increase H2O2-suppressed bcl-2 protein expression. Furthermore, Cim A and Z-lig suppressed the phosphorylation of p-38 but had no effect on phosphorylations of JNK, ERK and Akt in H2O2-stimulated neuronal cells. In the second part of the study, the effects of three medicinal herbs on proliferation of human H9-derived neural stem cells were tested. Only LCZ extracts could promote the proliferation of neural stem cells, as measured by MTT assays. It was further shown that LCZ extract enhanced the recovery after oxidative stress damage by H2O2 and nitric oxide. By a series of chemical separations, including solvent partition, column chromatography, and high performance liquid chromatography, a bioactive compound was isolated. It enhanced the proliferation of neural stem cells as measured by MTT and BrdU assays. The underlying mechanisms were investigated. It was found that Compound LCZ could induce the mRNA levels of CYP1B1 and HDAC9. However, these proteins did not play a role in enhanced proliferation of neural stem cells induced by Compound LCZ. Additionally, compound LCZ increased the phosphorylation of ERK but had no effect on phosphorylations of JNK, Akt and PI3K kinases. This activation of ERK correlated with the promotion of proliferation, as confirmed by an MEK inhibitor. Taken together, the study reveals that medicinal herbs LCX, BC and LCZ are potential drug candidates for treating oxidative stress related neurodegenerative diseases. Subjects: Materia medica Nervous system - Degeneration - T

Author: Girish Kumar Gupta
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 311036882X
Category : Science
Languages : en
Pages : 298

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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.