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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Neurodegenerative disorders encompass a broad range of sporadic and/or familial debilitating conditions characterized by the progressive dysfunction and loss of selective neuronal populations, determining different clinical phenotypes. Emerging research data indicate an interplay of genetic factors and epigenetic mechanisms underlying neurodegenerative processes, which lead to increased prevalence of neurodegenerative disorders. In concert with the constant increase in the aging population, neurodegenerative disorders currently represent a major challenge to public health worldwide. Despite recent advances in clinical and preclinical research, the pathogenesis of these disorders still remains poorly understood, without effective treatments being available to halt the neurodegenerative processes, but rather aiming at relieving symptoms. Therefore, a critical evaluation of current research data and in-depth understanding of the molecular mechanisms that lead to neurodegeneration are crucial in order to identify potential therapeutic targets that can pave the way to the development of novel and promising therapies. This Special Issue is focused on novel molecular data in the field of neurodegeneration that associate with the onset and progression of neurodegenerative diseases. We are particularly interested in original articles and reviews that provide new insights into the main molecular pathogenic mechanisms underlying neurodegenerative disorders, aiming to identify potential biomarkers and novel therapeutic strategies.
Neurodegenerative disorders encompass a broad range of sporadic and/or familial debilitating conditions characterized by the progressive dysfunction and loss of selective neuronal populations, determining different clinical phenotypes. Emerging research data indicate an interplay of genetic factors and epigenetic mechanisms underlying neurodegenerative processes, which lead to increased prevalence of neurodegenerative disorders. In concert with the constant increase in the aging population, neurodegenerative disorders currently represent a major challenge to public health worldwide. Despite recent advances in clinical and preclinical research, the pathogenesis of these disorders still remains poorly understood, without effective treatments being available to halt the neurodegenerative processes, but rather aiming at relieving symptoms. Therefore, a critical evaluation of current research data and in-depth understanding of the molecular mechanisms that lead to neurodegeneration are crucial in order to identify potential therapeutic targets that can pave the way to the development of novel and promising therapies. This Special Issue is focused on novel molecular data in the field of neurodegeneration that associate with the onset and progression of neurodegenerative diseases. We are particularly interested in original articles and reviews that provide new insights into the main molecular pathogenic mechanisms underlying neurodegenerative disorders, aiming to identify potential biomarkers and novel therapeutic strategies.
The complex etiology of neurodegenerative diseases is not fully understood, and the characterization of cellular pathways that are dysfunctional in these diseases is key for therapeutic development. Chemical and genetic perturbagens can probe cellular pathways to shed insight about both disease etiology and potential therapeutic targets. We analyzed the functional effects of chemical perturbagens in neurodegenerative disease models as evidenced by changes in transcriptomic, metabolomic, epigenomic, and proteomic data ("multi-omics" data). Our studies revealed novel modes of action for small molecule compounds that promote survival in a model of Huntington's Disease, a fatal neurodegenerative disorder. Integration of our multi-omics data using an interpretable network approach revealed that the autophagy and bioenergetics cellular pathways are affected by different sets of compounds that promote survival. Using staining and western blot assays, we validated the effect on autophagy for one set of compounds and found that the compounds activate this pathway. Using a cellular bioenergetics assay, we found that a second set of compounds shifts the bioenergetic flux from mitochondrial respiration to glycolysis, validating our network results. In a second study related to Huntington's Disease, we analyzed the effects of two peripheral huntingtin gene silencing techniques in mouse liver. We show that the transcriptional and metabolomic changes associated with both genetic silencing methods converge on similar cellular pathways, such as the immune response and fatty acid metabolism. As a whole, this thesis presents new insights into the functional effects of perturbagens that could impact neurodegenerative disease pathology and drug discovery.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Sirtuin Biology in Medicine: Targeting New Avenues of Care in Development, Aging, and Disease provides a fascinating and in-depth analysis of sirtuins in the body during normal physiology as well during disease highlighting the targeting of sirtuin-controlled pathways for the development of innovative, efficacious, and safe therapeutic strategies for multiple disorders in the body that ultimately can affect lifespan extension. Sirtuins are expressed throughout the body, have broad biological effects, and can significantly impact both cellular survival and longevity during acute and long-term illnesses. These histone deacetylases play an intricate role in the pathology, progression, and treatment of several disease entities ranging from neurodegenerative disorders, cardiovascular disease, immune system dysfunction, reproductive dysfunction, endocrine disorders, gastrointestinal disease, drug dependency, and aging-related disorders. Implementing a translational medicine format, this unique reference highlights novel signaling pathways for sirtuins that promote stem cell proliferation, enhance cellular protection, modulate pathways of apoptosis and autophagy, and extend life span. Each chapter is presented with insightful detail that will be of interest and a comprehensive resource to audiences that include scientists, physicians, pharmaceutical industry experts, nutritionists, and students. Chapters are authored by internationally recognized experts who discuss the broad role of sirtuins in health and disease Details the basic and clinical role of sirtuins for the development of new clinical treatments Summarizes the multidiscipline views and publications for the compelling discipline of sirtuins by covering systems throughout the body Serves as an important resource for a broad audience of healthcare providers, scientists, drug developers, and students in both clinical and research settings
Stroke is a major cause of death and the major cause of adult neurological disability in most of the world. Despite its importance on a population basis, research into the genetics of stroke has lagged behind that of many other disorders. However, the situation is now changing. Anincreasing number of single gene disorders causing stroke are being described, and there is growing evidence that polygenic factors are important in the risk of apparently "sporadic" stroke.Stroke Genetics provides an up-to-date review of the area, suitable for clinicians treating stroke patients, and both clinical and non-clinical researchers in the field of cerebrovascular disease. The full range of monogenic stroke disorders causing cerebrovascular disease, including ischaemicstroke, intracerebral haemorrhage, aneurysms and arteriovenous malformations, are covered. For each, clinical features, diagnosis, and genetics are described. Increasing evidence suggest that genetic factors are also important for the much more common multifactorial stroke; this evidence isreviewed along with the results of genetic studies in this area. Optimal and novel strategies for investigating multifactorial stroke, including the use of intermediate phenotypes such as intima-media thickness and MRI detected small vessel disease are reviewed. The book concludes by describing apractical approach to investigating patients with stroke for underlying genetic disorders. Also included is a list of useful websites.
Biochemical and Molecular Pharmacology in Drug Discovery comprises fundamental biochemical and molecular aspects of drug discovery and basic understanding of modern drug discovery approaches along with certain key topics related to molecular pharmacology of drugs and therapeutics. Molecular pharmacology has gained significant momentum among researchers, scientists, and academicians because of its increasing interest in drug discovery research across the globe. Molecular pharmacology involves a fundamental understanding of drug actions at the molecular level with the help of several tools and techniques of biochemical and molecular biology. It explains the phenomena of drug-target interactions considering different biochemical systems and cellular strategies. With the advent of technologies, current advances and research trends move toward molecular and/or target-based drug design and discovery. Through this book, readers will be able to gain skills and knowledge with a thorough understanding of the subject of biochemical and molecular pharmacology, in a comprehensive and systematic manner with special reference to recent advances in drug discovery research. Highlights the fundamentals of biochemical and molecular aspects, with reference to drug discovery research Depicts modern drug discovery approaches such as reverse pharmacology, drug repositioning, and CADD in the context of current research updates Summarizes recent developments in the molecular pharmacology of novel drugs/ therapeutic molecules
This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.