Download or read book The Trafficking and Metabolism of Amyloid Precursor Protein is Regulated by Its Cytoplasmic Carboxy terminus and by Adaptor Protein Interactions written by Gwendalyn DiAnn King and published by . This book was released on 2004 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cellular Trafficking and Metabolism of the Alzheimer s Disease Amyloid Precursor Protein APP in the Secretory and Endocytic Pathways written by Michelle Leigh Steinhilb and published by . This book was released on 2002 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Endocytic Protein Numb Regulates APP Metabolism and Notch Signaling written by George A. Kyriazis and published by . This book was released on 2008 with total page 84 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increased production of amyloid [beta] (A[beta]) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the [gamma]-secretase enzyme activity that involves the presenilin-1 protein in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a proline-rich region (PRR). Expression of these alternative spliced Numb transcripts is tightly regulated both temporally and spatially during development and aberrant Numb isoform expression has been associated with increased risk for cancers. Recent studies showed that the PTB domain of Numb interacts with the cytoplasmic tails of APP and Notch but the functional relevance of these interactions with respect to AD pathogenesis is not clear. In the current studies, we proposed to investigate the biological consequences of the interaction of the Numb proteins with APP and Notch in neural cells stably overexpressing each of the four human Numb proteins. Converging lines of evidence indicate that the endocytic pathway is involved in the aberrant processing of APP. Yet little is known about the underlying regulatory mechanism of APP endocytosis and trafficking. Elucidating the functional consequences of the interaction of APP with the Numb endocytic adapter proteins will provide a better understanding of the underlying mechanisms of aberrant APP processing. In the first part of our studies, we found that expression of the Numb isoforms lacking the insert in the PTB (SPTB-Numb) caused the abnormal accumulation of cellular APP in the early endosomes, and increased the levels of C-terminal APP fragments and A[beta]. By contrast, expression of the Numb isoforms with the insert in PTB (LPTB-Numb) leads to the depletion of cellular APP and coincides with significantly lower production of APP derivatives and A[beta]. The contrasting effects of the Numb isoforms on APP metabolism appeared to be independent of the composition of the PRR domain and were not attributed to differences in the expression of APP nor the activities of the various APP-processing secretases. Evidence is emerging that Notch signaling plays a role in the regulation of apoptosis in neural progenitors and in post-mitotic neurons. Numb has been shown to suppress Notch signaling by enhancing endocytosis and degradation of the Notch receptor. Whether the aberrant expression of the Numb isoforms leads to aberrant Notch signaling, and how this might promote neuronal degeneration is still not known. In the second part of our studies, we found that expression of SPTB-Numb protein enhances neuronal vulnerability to serum deprivation-induced cell death by a mechanism involving the dysregulation of cellular calcium homeostasis. Neural cells expressing SPTB-Numb exhibited markedly higher protein levels of transient receptor potential canonical 6 (TRPC6) channels and increased calcium entry in response to store depletion. These effects are mediated by Notch1 as pharmacological inhibition of Notch1 abrogated TRPC6 upregulation. We also found that serum deprivation increased TRPC6 upregulation by a mechanism dependent on Notch activation. Knockdown of TRPC6 expression stabilized intracellular calcium homeostasis and significantly suppressed serum deprivation-induced death suggesting that Notch-dependent TRPC6 upregulation contributes in part to serum-deprivation induced death. Interestingly, expression of LPTB-Numb protein suppressed serum deprivation-induced activation of Notch and the subsequent upregulation of TRPC6 and cell death. The latter finding further strengthens the link between the Numb isoform specific effect on Notch activation and the Notch-dependent upregulation of TRPC6. Finally, we showed that the Numb proteins differentially impact Notch activation by altering the endocytic trafficking and processing of Notch. Taken together, these studies demonstrate that aberrant expression of the Numb proteins may influence APP metabolism and Notch-mediated cellular responses to injury by altering their endocytic trafficking and processing.
Download or read book Magnesium in the Central Nervous System written by Robert Vink and published by University of Adelaide Press. This book was released on 2011 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: The brain is the most complex organ in our body. Indeed, it is perhaps the most complex structure we have ever encountered in nature. Both structurally and functionally, there are many peculiarities that differentiate the brain from all other organs. The brain is our connection to the world around us and by governing nervous system and higher function, any disturbance induces severe neurological and psychiatric disorders that can have a devastating effect on quality of life. Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level. The exact role and regulation of magnesium, in particular, remains elusive, largely because intracellular levels are so difficult to routinely quantify. Nonetheless, the importance of magnesium to normal central nervous system activity is self-evident given the complicated homeostatic mechanisms that maintain the concentration of this cation within strict limits essential for normal physiology and metabolism. There is also considerable accumulating evidence to suggest alterations to some brain functions in both normal and pathological conditions may be linked to alterations in local magnesium concentration. This book, containing chapters written by some of the foremost experts in the field of magnesium research, brings together the latest in experimental and clinical magnesium research as it relates to the central nervous system. It offers a complete and updated view of magnesiums involvement in central nervous system function and in so doing, brings together two main pillars of contemporary neuroscience research, namely providing an explanation for the molecular mechanisms involved in brain function, and emphasizing the connections between the molecular changes and behavior. It is the untiring efforts of those magnesium researchers who have dedicated their lives to unraveling the mysteries of magnesiums role in biological systems that has inspired the collation of this volume of work.
Download or read book Sonic Hedgehog Signaling Pathway in Amyloid Precursor Protein Trafficking and Proteolysis written by Anna Gennadiy Vorobyeva and published by . This book was released on 2014 with total page 416 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) is the most common form of dementia for which there is no cure. AD is characterized by progressive neurotoxicity resulting in cell death and cognitive decline. Two hallmarks responsible for the aforementioned neuropathology are senile plaques and neurofibrillary tangles composed of Amyloid-Beta; (A-Beta) peptide and hyperphosphorylated tau protein, respectively. A-Beta; is produced from regulated proteolysis of Amyloid precursor protein (APP). Alterations to this process can results in increased A-Beta; deposition resulting in AD pathogenesis. Here we discovered that cyclopamine, a plant sterol, modulates APP metabolism by altering APP subcellular trafficking. Cyclopamine treatment alters retrograde trafficking of APP C-terminal fragments (CTFs) after endocytosis, thereby decreasing A-Beta; generation. This raises the possibility that cyclopamine may ameliorate AD-like pathologies in other AD animal models. We addressed the possibility that cyclopamine's target, Smoothened (Smo), can alter APP metabolism and discovered a likely novel regulatory role for Smo. Smo is a component of the Sonic hedgehog (Shh) signaling pathway, which requires the primary cilium for canonical mammalian Shh signaling. Pharmacological and genetic analysis lead us to believe several Shh signaling components modulate APP proteolysis via a previously uncharacterized noncanonical Shh mechanism. Collectively these findings lead us to investigate the possibility that APP colocalizes with Shh signaling components to the primary cilia and whether or not primary cilia respond to extracellular A-Beta; levels. We discovered APP colocalized with Smo to primary cilia and that primary cilia were significantly compromised upon A-Beta; treatment. Collectively, this thesis provides significant insight into APP proteolysis through regulating trafficking events. Modulating APP trafficking opens a novel avenue to address A-Beta; production. In addition, we discovered a novel target for AD therapeutics; the Shh signaling pathway.
Download or read book Neuronal Cytoskeleton written by Hirokawa and published by CRC Press. This book was released on 1994-01-12 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the primary functions of microtubule-associated proteins (MAPs) such as MAP2 and tau in neuronal morphogenesis, as well as relationships between neuronal differentiation and the expression of neuronal intermediate filaments (nestin, alpha internexin, and neurofilament triplet proteins). It emphasizes the importance of several cytoskeletal proteins for neuronal differentiation and morphogenesis, organelle transport, and synaptic functions. The book considers the involvement of tau MAPs in the formation of paired helical filaments in Alzheimer's disease, and it examines the mechanisms of organelle transports and molecular motors such as kinesin, braindynein, and kinesin superfamily proteins. Cytoskeletal proteins involved in synaptic formation and transmitter release and new synaptic junctional-associated proteins are explored as well.
Download or read book Genomics Circuits and Pathways in Clinical Neuropsychiatry written by Thomas Lehner and published by Academic Press. This book was released on 2016-06-07 with total page 798 pages. Available in PDF, EPUB and Kindle. Book excerpt: This foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates discoveries of specific genes and genomic regions associated with these conditions, the genetic and anatomic architecture of these syndromes, and addresses how recent advances in genomics are leading to a reappraisal of the biology underlying clinical neuroscience. In doing so, it critically examines the promise and limitations of these discoveries toward treatment, and to the interdisciplinary nature of understanding brain and behavior. Coverage includes new discoveries regarding autism, epilepsy, intellectual disability, dementias, movement disorders, language impairment, disorders of attention, schizophrenia, and bipolar disorder. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry focuses on key concepts, challenges, findings, and methods in genetics, genomics, molecular pathways, brain circuitry, and related neurobiology of neurologic and psychiatric disorders. Provides interdisciplinary appeal in psychiatry, neurology, neuroscience, and genetics Identifies key concepts, methods, and findings Includes coverage of multiple disorders from autism to schizophrenia Reviews specific genes associated with disorders Discusses the genetic architecture of these syndromes Explains how recent findings are influencing the understanding of biology Clarifies the promise of these findings for future treatment
Download or read book Endoplasmic Reticulum Stress in Health and Disease written by Patrizia Agostinis and published by Springer Science & Business Media. This book was released on 2012-08-13 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.
Download or read book Neurodegenerative Diseases written by Uday Kishore and published by BoD – Books on Demand. This book was released on 2013-05-15 with total page 642 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neurobiology of Acupuncture written by and published by Academic Press. This book was released on 2013-11-07 with total page 363 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book summarises the recent development in acupuncture research and in particular, the neurobiology of acupuncture. It provides a focus but a diverse range of subjects covering many body systems. The first a few chapters discuss the basic principles of acupuncture, then its modulatory effects on nervous system such as induction of neurotrophin and neurogenesis in the brain. Late chapters explore the clinical effects and potential mechanisms of acupuncture on different conditions ranging from neurological diseases such as Parkinson’s, Alzheimer’s, and stroke, to psychiatric illnesses, insomnia, hypertension, gastrointestinal diseases and drug addiction. We believe this will promote the understanding acupuncture treatment and enhance acupuncture research in the future. This volume of International Review of Neurobiology brings together cutting-edge research on the neurobiology of acupuncture It reviews current knowledge and understanding, provides a starting point for researchers and practitioners entering the field, and builds a platform for further research and discovery
Download or read book Methods of Behavior Analysis in Neuroscience written by Jerry J. Buccafusco and published by CRC Press. This book was released on 2000-08-29 with total page 341 pages. Available in PDF, EPUB and Kindle. Book excerpt: Using the most well-studied behavioral analyses of animal subjects to promote a better understanding of the effects of disease and the effects of new therapeutic treatments on human cognition, Methods of Behavior Analysis in Neuroscience provides a reference manual for molecular and cellular research scientists in both academia and the pharmaceutic
Download or read book Cyclin Dependent Kinase 5 Cdk5 written by Nancy Y. Ip and published by Springer Science & Business Media. This book was released on 2009-02-28 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Encyclopedia of Signaling Molecules written by Sangdun Choi and published by Springer. This book was released on 2017-12-15 with total page 6330 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of this encyclopedia presents over 400 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities.
Download or read book Dissertation Abstracts International written by and published by . This book was released on 2004 with total page 882 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Neurodegeneration and Alzheimer s Disease written by Ralph N. Martins and published by John Wiley & Sons. This book was released on 2019-07-10 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the impact of diet, exercise, genetics, and hormones on the risk and development of Alzheimer’s and other neurogenerative diseases Diet is widely known to impact on neurological function. Nevertheless, academic texts discussing this relationship are relatively few in number. This book therefore fills an important gap in the current literature. Opening with an overview of neurodegenerative diseases, particularly Alzheimer’s disease, the text then focuses on explaining the means by which glycemic control and lipid metabolism – and associated nutritional and lifestyle variables – may factor into such disorders’ prevention and treatment. An international group of experts in the fields of food science and neurodegeneration have contributed chapters that examine Alzheimer’s disease within a broad range of contexts. Offering dietary, genetic, and hormonal perspectives, the authors explore topics ranging from sugar consumption to digestive fermentation, and Alzheimer’s disease animal models to the cognition-enhancing effects of physical exercise. Also included are overviews of the latest research into current and developing methods of treatment and diagnosis, as well as differential diagnostics. This groundbreaking book: Explores how glucose metabolism, insulin resistance, lipid metabolism, and high intake of refined carbohydrates are linked to Alzheimer's disease Discusses how genetic makeup can impact risk of Alzheimer’s and Parkinson’s disease Examines cognitive changes in neurodegeneration, lists current tests for determining cognitive impairment, and provides information concerning differential diagnosis Discusses potential advantages of increasing antioxidant and micronutrient intake Reviews hormonal influences on neurodegeneration Examines the links between protein intake and Alzheimer’s disease. Neurodegeneration and Alzheimer's Disease is an essential resource for researchers, medical practitioners, dietitians, and students with an interest in neurological diseases and their diagnosis and risk factors, as well as diet-related conditions such as diabetes and obesity. Lifestyle and diet influence neurodegeneration risk, and a better understanding of this evidence amongst health professionals will hopefully lead to greater public awareness of how to reduce the likelihood of these widespread conditions.
Download or read book Synaptic Function written by Neurosciences Institute (New York, N.Y.) and published by Wiley-Interscience. This book was released on 1987 with total page 808 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book consists of five sections. The first section details methods for analyzing both presynaptic and postsynaptic function and emphasizes the molecular aspects of synapses. It describes ongoing studies of neurotransmitter release, voltage- sensitive ion channels, and electronic transmission at gap junctions. The second section focuses on the growing menagerie of neurotransmitters: their catagorization into chemical families, their relation to ion channels, their modulation by second messenger systems and their role in pharmacologic action. The third section considers the important relationship of transmitter diversity and synaptic types to the behavior of actual cellular networks. All of the studies described in these sections point to the necessity of considering interactions between anatomy, chemistry, physiology and pharmacology if synaptic function is to be understood at any one of these levels of analysis.
