Metabolic and Bioenergetic Drivers of Neurodegenerative Disease: Neurodegenerative Disease Research and Commonalities with Metabolic Diseases PDF Download
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Author:
Publisher: Academic Press
ISBN: 0128201266
Category : Medical
Languages : en
Pages : 458
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Book Description
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
Author:
Publisher: Academic Press
ISBN: 0128201266
Category : Medical
Languages : en
Pages : 458
Get Book
Book Description
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
Author:
Publisher: Academic Press
ISBN: 012823122X
Category : Medical
Languages : en
Pages : 322
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Book Description
Metabolic Drivers and Bioenergetic Components of Neurodegenerative Disease reviews how the different aspects of metabolic dysfunction and consequent pathology associated with neurodegenerative diseases, including Alzheimer’s and Parkinson’s, can be targeted by novel treatment approaches. Topics covered include Cellular Senescence in Aging and Age-Related Disorders: Implications for Neurodegenerative Diseases; Repurposing GLP1 agonists for Neurodegenerative Diseases; Ketotherapeutics for Neurodegenerative Diseases; Enhancing Mitophagy as a Therapeutic Approach for Neurodegenerative Diseases; Harnessing Neurogenesis in the Adult Brain – A Role in Type 2 Diabetes Mellitus and Alzheimer’s disease; and much more. Summarizes the impact of the metabolic hypothesis on underlying mechanisms of neurodegenerative diseases Presents novel, potential treatment strategies based on the metabolic hypothesis for neurodegenerative diseases
Author: Christian Behl
Publisher: Springer Nature
ISBN: 3031315707
Category : Medical
Languages : en
Pages : 661
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Book Description
This book highlights the key phases and central findings of Alzheimer’s Disease research since the introduction of the label ‘Alzheimer’s Disease’ in 1910. The author, Christian Behl, puts dementia research in the context of the respective zeitgeist and summarizes the paths that have led to the currently available Alzheimer’s drugs. As the reader is taken through the major developments in Alzheimer's Disease research, particularly over the past thirty years, Behl poses critical questions: Why are the exact causes of Alzheimer's Disease still in the dark, despite all the immense, worldwide research efforts in academia as well as in the pharmaceutical industry? Why has the majority of an entire research field kept focusing on a single hypothesis that establishes the deposition of the amyloid beta peptide in the brain as the key trigger of Alzheimer's pathology, even though this concept has still not been convincingly proven in the clinics? Are there other hypotheses that might explain the pathogenesis of this complex brain disease, and if so, why were these perspectives not adequately followed? In this book, Behl tries to answer these questions. Starting with the historical background, the author illustrates the long and arduous research journey, its numerous setbacks, and the many alternative explanations for the disease, which have started gaining increasing attention and acceptance in the Alzheimer’s research community only more recently. With his deep dive into the history and progression of this research, including the most recent developments, Behl explains why he believes that it is high time to promote a paradigm shift in Alzheimer’s Disease research. The book is written for all researchers in the fields of neurobiology and neurodegeneration, as well as other biomedical fields, who would like to gain a broad and beyond the surface insight into (the key developments of) one of the most promoted research fields of our time. With its extensive literature references and over 100 illustrations, the book is also attractive for students and interested lay persons. Elaborating on all the different aspects and research approaches of this research field, the author aims to convince the reader that the underlying causes of Alzheimer’s Disease may be much more complex than previously thought and that this must be considered for future research directions. While he hopes that the Alzheimer’s research community is finally ready to shed its ‘amyloid-straitjacket’ that has hampered progress for too long, he is also convinced that a much-needed paradigm shift can guide future Alzheimer’s Disease research and provide a new and broader perspective on this age-dependent brain disease.
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: Marie-Francoise Chesselet
Publisher: Springer Science & Business Media
ISBN: 1592590063
Category : Medical
Languages : en
Pages : 416
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Book Description
With the unprecedented identification of new mutation mechanisms in neurodegenerative diseases and the emergence of common mechanisms among diseases that were once considered unrelated, neurobiologists are poised for the development of new therapies based on high throughput screenings and a better understanding of the molecular and cellular mechanisms leading to neurodegeneration. In Molecular Mechanisms of Neurodegenerative Diseases, Marie-Francoise Chesselet, MD, PhD, and a panel of leading researchers and neurologists from industry and academia critically review the most recent advances from different yet complementary points of view. Focusing on Alzheimer's, Parkinson's, and CAG triplet repeat diseases, the authors show how studies of cellular and genetically engineered animal models have enhanced our understanding of the molecular mechanisms of neurodegenerative diseases and may lead to the development of new therapeutics. Topics include the role of Ab toxicity, glial cells, and inflammation in Alzheimer's disease; the formation of abnormal protein fragments across several diseases, the impact of dopamine and mitochondrial dysfunction on neurodegeneration; and the potential of genetics to identify the molecular mechanisms of neurodegenerative diseases. Authoritative and insightful, Molecular Mechanisms of Neurodegenerative Diseases synthesizes the novel ideas and concepts now emerging to create a fresh understanding of neurodegenerative disorders, one that promises to lead to powerful new therapies that prevent, delay the onset, slow the progression, or even cure these cruel diseases.
Author: Amy Katherine Reeve
Publisher: Springer
ISBN: 9780857297006
Category : Medical
Languages : en
Pages : 242
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Book Description
As age related diseases increase in prevalence and impact more significantly on medical resources it is imperative to understand these diseases and the mechanisms behind their progression. New research has stimulated a growing interest in mitochondrial involvement in neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis and the mechanisms which lead from mitochondrial dysfunction to neurodegeneration. Mitochondrial Dysfunction in Neurodegenerative Disorders brings together contributions from leaders in the field internationally on the various ways in which mitochondrial dysfunction contributes to the pathogenesis of these diseases, guiding the reader through the basic functions of mitochondria and the mechanisms that lead to their dysfunction, to the consequences of this dysfunction on neuronal function before finishing with the modelling of these disorders and discussion of new potential therapeutic targets. Mitochondrial Dysfunction in Neurodegenerative Disorders provides an accessible, authoritative guide to this important area for neurologists; research and clinical neuroscientists; neuropathologists; and residents with an interest in clinical research.
Author: Nancy Y. Ip
Publisher: Springer Science & Business Media
ISBN: 0387788875
Category : Medical
Languages : en
Pages : 326
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Book Description
Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.
Author: Valerie Sackmann
Publisher: Linköping University Electronic Press
ISBN: 9175190125
Category :
Languages : en
Pages : 60
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Book Description
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases with rates increasing along with the ageing global population. Despite best efforts, we still do not understand the etiopathogenesis of these diseases and there are no effective disease-modifying treatments. Cognitive deficiencies or motor complications that emerge during AD and PD are thought to be the result of the accumulation of misfolded, aggregate-prone proteins, such as amyloid-? (A?) and tau or ?-synuclein (?-syn), respectively. Growing evidence suggests that prefibrillar oligomers of A? and ?-syn (oA? and o?-syn) are key contributors to the progression of these diseases. The progressive accumulation of these proteins leads to a gradual spread of pathology throughout interconnected brain regions, but the mechanisms by which this spreading occurs are still largely unknown. Neuroinflammation has been recognised as an important contributor to neurodegenerative disease. It is hypothesised that a pro-inflammatory environment initiated by the innate immune system, either through activation from A? itself or indirectly through neuronal injury signals in AD. These phenomena are thought to either cause or accelerate AD, such that an anti-inflammatory approach may be neuroprotective. In paper I, we investigated whether different inflammatory environments affected the transfer of oA? between neuron-like cells, in addition to investigating inter- and intracellular protein changes. This study demonstrated that an anti-inflammatory environment reduces the transfer of oA? between cells. We also provide evidence that these cells begin to take on the “phenotype” of the inflammatory milieu, while also demonstrating that the expression profile of endosomal/lysosomal and protein trafficking proteins is altered during these conditions. Small extracellular vesicles called exosomes, which are key players in cell to cell communication, have been proposed to play an influential role in spreading neurodegenerative proteins between cells. Exosomes are small membranous vesicles that are formed by the inward budding of multivesicular bodies (MVBs). These MVBs can then merge with the plasma membrane to be released into the extracellular environment as vesicles, which serve as vehicles for transferring proteins, lipids, and mRNAs between cells. The ESCRT-dependent pathway is the most understood mechanism underlying exosome biogenesis. However, exosomes can also be formed through ESCRT-independent pathways, including through the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2), which produces ceramide. Paper II investigated whether exosomes formed through an ESCRT-independent pathway plays a significant role in the transfer of o?-syn between neuron-like cells. As oxidative stress is a common feature in PD brains, which in turn dysregulates nSMase2 activity, we also tested our model under hypoxic conditions. Inhibition of nSMase2 significantly reduced the transfer of o?-syn between cells but also resulted in decreased ?-syn aggregation. Hypoxia did not influence o?-syn transfer, however, it significantly dysregulated the sphingolipid composition, which may be important for ?-syn binding to exosomes and exosome communication. During AD and PD, there is a noted reduction in the effectiveness of autophagy, a process critical to cellular proteostasis. Recent studies have uncovered shared regulatory mechanisms of exosome biogenesis and autophagy, suggesting that they are closely linked. Previous findings have shown that inhibition of autophagy in AD mice mediates A? trafficking through altering the secretion of A? in MVBs. To further study this effect, we investigated the interplay between autophagy and exosome secretion using ATG7 knock-out x APPNL-F knock-in AD mice in paper III. These autophagy-deficient AD mice had a reduced extracellular A? plaque load, but increased intracellular A?, which was found to be assembled into higher-ordered assemblies. While exosomal secretion was dysregulated in these mice, the amount of A? packaged into the exosomes was unchanged. Lastly, one of the biggest challenges in developing effective treatments for AD is the lack of early diagnosis of living patients. As the connection between exosomes and the spread of neurodegenerative proteins is still relatively new, there remains a diagnostic potential to be explored with exosomes. Paper IV aimed to develop a new diagnostic assay to detect oA? in exosomes isolated from human cerebrospinal fluid. Although exosomal oA? was readily detected in some of these samples, the assay’s sensitivity requires additional optimisation before it can be further validated for the clinic. In summary, the studies presented in this thesis have furthered our understanding of how inflammation, autophagy, and exosomes contribute to the intercellular transmission of AD and PD associated proteins. We have shown that an anti-inflammatory approach may slow down the progression of AD through reducing the transfer of oA? between cells. We also provide novel findings relating to the biogenesis of exosomes, which in turn affected the ability of exosomes to transmit neurodegenerative proteins between cells, and their association with autophagic processes. Finally, we have investigated the feasibility of exosomes as an early AD diagnostic marker. This work has helped to elucidate some of the mechanisms underlying the progression of neurodegenerative diseases, which may be useful targets for the investigation of new therapeutic avenues.
Author: Nenad Blau
Publisher: Springer
ISBN: 3642403379
Category : Medical
Languages : en
Pages : 880
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Book Description
This book, combining and updating two previous editions, is a unique source of information on the diagnosis, treatment, and follow-up of metabolic diseases. The clinical and laboratory data characteristic of rare metabolic conditions can be bewildering for both clinicians and laboratory personnel. Reference laboratory data are scattered, and clinical descriptions may be obscure. The Physician’s Guide documents the features of more than five hundred conditions, grouped according to type of disorder, organ system affected (e.g. liver, kidney, etc) or phenotype (e.g. neurological, hepatic, etc). Relevant clinical findings are provided and pathological values for diagnostic metabolites highlighted. Guidance on appropriate biochemical genetic testing is provided. Established experimental therapeutic protocols are described, with recommendations on follow-up and monitoring. The authors are acknowledged experts, and the book will be a valuable desk reference for all who deal with inherited metabolic diseases.
Author: Agustín Ibáñez
Publisher: Frontiers Media SA
ISBN: 2889454940
Category :
Languages : en
Pages : 217
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Book Description
Neurodegenerative diseases are the most frequent cause of dementia, representing a burden for public health systems (especially in middle and middle-high income countries). Although most research on this issue is concentrated in first-world centers, growing efforts in South America are affording important breakthroughs. This emerging agenda poses new challenges for the region but also new opportunities for the field. This book aims to integrate the community of experts across the globe and the region, and to establish new challenges and developments for future investigation. We present research focused on neurodegenerative research in South America. We introduce studies assessing the interplay among genetic, neural, and behavioral dimensions of these diseases, as well as articles on vulnerability factors, comparisons of findings from various countries, and works promoting multicenter and collaborative networking. More generally, our book covers a broad scope of human-research approaches (behavioral assessment, neuroimaging, electromagnetic techniques, brain connectivity, peripheral measures), animal methodologies (genetics, epigenetics, proteomics, metabolomics, other molecular biology tools), species (all human and non-human animals, sporadic, and genetic versions), and article types (original research, review, and opinion papers). Through this wide-ranging proposal, we hope to introduce a fresh approach to the challenges and opportunities of research on neurodegeneration in South America.
