Download or read book Golgi Pathology in Neurodegenerative Diseases written by Catherine Rabouille and published by Frontiers Media SA. This book was released on 2016-03-09 with total page 121 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Golgi apparatus is a central organelle that lies at the heart of the secretory pathway. It ensures post-translational protein modifications such as glycosylation and cleavage as well as protein sorting to neuronal axons and dendrites. Structural and functional alterations of the Golgi apparatus (fragmentation and atrophy), which are collectively termed Golgi pathology, are now recognized as a constant feature of many neuro-degenerative diseases. However, the molecular mechanisms underlying these changes and their precise relevance to neurodegeneration have not yet been completely elucidated. This eBook contains 13 reviews that address the molecular mechanisms of Golgi pathology in Parkinson and Alzheimer diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies, and discuss their potential relevance to the pathological loss of neuronal cell bodies, axons and synapses.
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 Neuropathology of Neurodegenerative Diseases written by Gabor G. Kovacs and published by Cambridge University Press. This book was released on 2017-12-13 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: This practical guide to the diagnosis of neurodegenerative diseases discusses modern molecular techniques, morphological classification, fundamentals of clinical symptomology, diagnostic pitfalls and immunostaining protocols. It is based on the proteinopathy concept of neurodegenerative disease, which has influenced classification and provides new strategies for therapy. Numerous high-quality images, including histopathology photomicrographs and neuroradiology scans, accompany the description of morphologic alterations and interpretation of immunoreactivities. Diagnostic methods and criteria are placed within recent developments in neuropathology, including the now widespread application of immunohistochemistry. To aid daily practice, the guide includes diagnostic algorithms and offers personal insights from experienced experts in the field. Special focus is given to the way brain tissue should be handled during diagnosis. This is a must-have reference for medical specialists and specialist medical trainees in the fields of pathology, neuropathology and neurology working with neuropathologic features of neurodegenerative diseases.
Download or read book Handbook of Research on Critical Examinations of Neurodegenerative Disorders written by Uddin, Md. Sahab and published by IGI Global. This book was released on 2018-07-31 with total page 621 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurodegeneration is a key feature of several diseases that are referred to as neurodegenerative diseases. The process of neurodegeneration is not well-understood so the diseases that stem from it have, as yet, no cures. As such, studying the effects of these disorders can provide insight into the treatment, prevention, and future opportunities and challenges in this growing field. The Handbook of Research on Critical Examinations of Neurodegenerative Disorders is a critical scholarly resource that provides an extensive explanation of various neurodegenerative disorders based on existing studies to clarify etiology, pathological mechanisms, diagnosis, therapeutic interventions, as well as current status and future opportunities and challenges. Featuring coverage on a broad range of topics such as dementia, mitochondrial dysfunction, and risk factors, this book is geared towards neurobiologists, neuropsychologists, neurophysiologists, neuropathologists, medical professionals, academicians, and researchers seeking research on the complexity of neurodegenerative disorders.
Download or read book Golgi Dynamics in Physiological and Pathological Conditions written by Jaakko Saraste and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Articles in this collection illustrate our recent progress in understanding Golgi biology, and also outline a specific set of yet unanswered Golgi-related questions. For example, exactly how do cargo and resident proteins travel to, through and out of the Golgi? What are the exact modes, carriers and molecular machineries of bi-directional Golgi trafficking? How are Golgi structure and its various functions modified during normal (differentiation, development, etc.) and abnormal (diseases, drugs, pathogens, etc.) circumstances?
Download or read book Leucine Rich Repeat Kinase 2 LRRK2 written by Hardy J. Rideout and published by Springer. This book was released on 2017-03-28 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cerebrospinal Fluid Biomarkers written by Charlotte E. Teunissen and published by Humana. This book was released on 2022-05-19 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the latest methods used in clinical neurochemistry laboratories for both clinical practice and research. Chapters in this book discuss topics such as techniques for cerebrospinal fluid (CSF) collection, pre-analytical processing, and basic CSF analysis; an examination of biomarkers including ELISA and automated immunochemical assays for amyloid and tau markers for Alzheimer’s disease; the analysis of neurofilaments by digital ELISA; and an example of successful novel immunoassay development. In the Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and thorough, Cerebrospinal Fluid Biomarkers is a valuable resource for clinicians and researchers to use in CSF labs and CSF courses.
Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
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 The Golgi Apparatus written by Eric G. Berger and published by Springer Science & Business Media. This book was released on 1997 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: In 1898 Camillo Golgi reported his newly observed intracellular structure, the apparato reticolare interno, now universally known as the Golgi Apparatus. The method he used was an ingenious histological technique (La reazione nera) which brought him fame for the discovery of neuronal networks and culminated in the award of the Nobel Prize for Physiology and Medicine in 1906. This technique, however, was not easily reproducible and led to a long-lasting controversy about the reality of the Golgi apparatus. Its identification as a ubiquitous organelle by electron microscopy turned out to be the breakthrough and incited an enormous wave of interest in this organelle at the end of the sixties. In recent years immunochemical techniques and molecular cloning approaches opened up new avenues and led to an ongoing resurgence of interest. The role of the Golgi apparatus in modifying, broadening and refining the structural information conferred by transcription/translation is now generally accepted but still incompletely understood. During the coming years, this topic certainly will remain center stage in the field of cell biology. The centennial of the discovery of this fascinating organelle prompted us to edit a new comprehensive book on the Golgi apparatus whose complexity necessitated the contributions of leading specialists in this field. This book is aimed at a broad readership of glycobiologists as well as cell and molecular biologists and may also be interesting for advanced students of biology and life sciences.
Download or read book Progressive Brain Disorders in Childhood written by Juan M. Pascual and published by Cambridge University Press. This book was released on 2017-04-20 with total page 507 pages. Available in PDF, EPUB and Kindle. Book excerpt: A review of childhood neurodegenerative and other progressive but non-degenerative disorders to guide their diagnosis and management.
Download or read book The Neuronal Ceroid Lipofuscinoses Batten Disease written by Sara Mole and published by OUP Oxford. This book was released on 2011-03-10 with total page 772 pages. Available in PDF, EPUB and Kindle. Book excerpt: The neuronal ceroid lipofuscinoses are an extremely rare group of inherited neurodegenerative diseases that primarily affect children. Core symptoms of these conditions typically include epilepsy, cognitive decline and visual failure. These diseases are so rare that professionals who come into contact with them need a consultative reference work that enables them to become expert, or identify who to contact for more details. Fully updated and revised, this second edition continues to be the definitive volume on this devastating group of disorders. Written by an international collection of authorities in the field, it provides invaluable advice on their diagnosis, patient care, and new treatments that are available. This new edition of the definitive reference text on the neuronal ceroid lipofuscinoses will prove useful for clinicians, family physicians, research scientists, diagnostic laboratories, families affected by the disease as well as by workers in industry planning translational research.
Download or read book The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes written by Valerie Sackmann and published by Linköping University Electronic Press. This book was released on 2019-10-16 with total page 69 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Tau oligomers written by Jesus Avila and published by Frontiers E-books. This book was released on 2014-08-18 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.
Download or read book Molecular Pathology of Alzheimer s Disease written by Rudy Castellani and published by Biota Publishing. This book was released on 2013-10-01 with total page 93 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer’s Disease is characterized pathologically by two principal hallmark lesions: the senile plaque and the neurofibrillary tangle. Since the identification of each over 100 years ago, the major protein components have been elucidated. This has led in turn to the elaboration of metabolic cascades involving amyloid-β production in the case of the senile plaque, and phosphorylated-tau protein in the case of the neurofibrillary tangle. The pathogenesis and histogenesis of each have been the source of extensive investigation and some controversy in recent years, as both cascades have been implicated in the pathogenesis of Alzheimer’s Disease, relied upon in the diagnostic criteria for Alzheimer’s Disease at autopsy, and targeted for therapeutic intervention. With the accumulation of data and expansion of knowledge of the molecular biology of Alzheimer’s Disease, it appears that the enthusiasm for successful intervention has been premature. In this book, we detail the discovery and characterization of the major pathological lesions, their associated molecular biology, their relationship to clinical disease, and potential fundamental errors in understanding that may be leading scientific investigators in unintended directions.
Download or read book Neurodegenerative Diseases written by Shamim I. Ahmad and published by Springer Science & Business Media. This book was released on 2012-03-12 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Proteostasis and Disease written by Rosa Barrio and published by Springer Nature. This book was released on 2020-04-09 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, written by members of the European network PROTEOSTASIS, provides an up-to-date review of the research regarding protein homeostasis in health and disease. With new discoveries contributing to the increasing complexity of this topic, the book offers a detailed overview of the pathways regulating protein homeostasis, including autophagy and the ubiquitin protein family. Following a basic introduction, it explains how defects in protein homeostasis contribute to numerous pathologies, including cancer, neurodegeneration, inflammation and a number of rare diseases. In addition, it discusses, the role of protein homeostasis in cellular development and physiology. Highlighting the latest research in the field of protein homeostasis and its implications for various clinically relevant diseases, the book appeals to researchers and clinicians, while also offering a reference guide for scholars who are new to the field.