Metabolic And Bioenergetic Drivers Of Neurodegenerative Disease Neurodegenerative Disease Research And Commonalities With Metabolic Diseases

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

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

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.

This book aims to provide a state-of-the-art summary of what is currently known about brain glycogen metabolism, detailing the recent advances in our understanding of why glycogen is so critical for normal brain function. The role of glycogen in cellular neurophysiology remains largely unclear and its specific contribution to the energy demand of brain cells is still elusive.Glycogen is the sole cerebral glucose reserve and is emerging as a fundamental component of brain energy metabolism. Pharmacological or genetic manipulation of glycogen metabolism in the brain impairs memory formation and increases susceptibility to epileptic seizures and cortical spreading depression. Glycogen is also directly implicated in abnormal neuronal excitability and mental retardation that characterize brain disorders like Lafora disease and Pompe disease.

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.

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.

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.

Metabolic syndrome is a set of risk factors that includes: abdominal obesity, a decreased ability to process glucose (insulin resistance), dyslipidemia (unhealthy lipid levels), and hypertension. Patients who have this syndrome have been shown to be at an increased risk of developing cardiovascular disease and/or type 2 diabetes. Metabolic syndrome is a common condition that goes by many names (dysmetabolic syndrome, syndrome X, insulin resistance syndrome, obesity syndrome, and Reaven's syndrome). This is the first book to fully explain the relationships between psychiatric illness, Metabolic Syndrome, diet, sleep, exercise, medications, and lifestyle choices. Metabolic Syndrome is a major risk factor in Major Depression, Alzheimer's Disease, Sleep Disorders, Sexual Dysfunction, Fibromyalgia, and several other illnesses of psychiatric significance. Conversely, some psychiatric illnesses tend to predispose patients to Metabolic Syndrome. Of further interest is the fact that some of the medications used in the treatment of psychiatric illnesses have been found to cause or exacerbate Metabolic Syndrome. The author here provides basic information about what genetic predispositions, medical conditions, and lifestyle choices make Metabolic Syndrome more likely to occur. Among the contributing factors that are discussed are genetics, habitual intake of high glycemic index carbohydrates, fructose, saturated fats, trans fatty acids, vitamins, micronutrients, obesity, smoking, and lack of exercise. The author describes the actual mechanisms by which Metabolic Syndrome progresses and causes damage in the body, including the action of insulin and the pathophysiology of insulin resistance. Details are provided on what occurs in the liver, pancreas, muscle, fat cells, and immune system as Metabolic Syndrome progresses. New findings are presented on fat cells, including the fact that they are beginning to be considered as endocrine cells. There is a substantive discussion of leptin, which is one of the important adipocytokines. Also carbohydrate, 'bad fats', inflammation, oxidative damage, over-stimulation of the 'fight or flight' system, and high levels of the stress hormone cortisol can actually cause the manifestations of Metabolic Syndrome. These explanations set the stage for an explanation of the inter-relationships between Metabolic Syndrome, psychiatric illness, dementia and effects of not only diet and life choices, but also the effects of psychiatric medications. Finally, there is an important and unique section on the relationship between Metabolic Syndrome and various psychiatric illnesses, and how they exacerbate each other. The significance of Metabolic Syndrome in Major Depression, Bipolar Affective Disorder, Schizophrenia, fibromyalgia and Polycystic Ovary Disease is vast and it is important to realise the effects of psychiatric medications on Metabolic Syndrome. The author discusses antidepressants, mood stabilizers and the new atypical antipsychotics. There are dramatic differences among medications in the way they affect Metabolic Syndrome and pharmaceutical companies will want to promote patient awareness with this book.