Download or read book Molecular Intervention in Mouse Models of Amyotrophic Lateral Sclerosis and Alzheimer s Disease written by Steven Prescott Bennett and published by . This book was released on 2009 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABSTRACT: Neurodegeneration describes the progressive loss of structure and function of neurons, leading ultimately to cell and organism death. Although the initiating factors of neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis may be different, they share common pathophysiologies. Proteinopathies, as these diseases are now termed, are characterized by atypical deposits of proteins, often due to misfolding. Associated with these deposits are dysfunctional mitochondria, oxidative stress, disrupted axonal transport, inflammation, and apoptotic cell death. If this occurs in motor neurons, as in ALS, ataxia precedes death with little or no change in cognition. On the other hand, if the deposits are found in cortical neurons, as in Alzheimer's disease, the outcome is dementia and motor function remains largely intact. Each disease is selective for particular types of neurons and brain regions. Although research has elucidated much of the molecular biology involved in these diseases, their initiating causes remain largely unknown. Most of our current understanding originated with the identification of gene mutations that cause rare familial forms of these diseases. As a result, numerous strains of transgenic animals have been developed to study neurodegenerative disease phenomena and were central to the studies presented in this body of work. Novel routes of drug and gene delivery are described here as well as characterization of the mouse models studied. In particular, this work demonstrates that the blood brain barrier is disrupted in ALS followed by the formation of autorosettes in ALS mice. In various Alzheimer's disease mouse models, it was demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT) not only interacts with amyloid plaques, but also induces tau phosphorylation in vivo; tying together these disease hallmarks. It was also shown that small fragments of amyloid beta (1-11) could disrupt the formation of mature amyloid plaques in these mice. Lastly, it was demonstrated that mature plaques could also be decreased by intracranial delivery of granulocyte-macrophage stimulating factor (GM-CSF). My dissertation research goal was to understand and develop these treatment strategies based on protein disaggregation, neuroprotection, and inflammation, meanwhile developing novel methods for targeted delivery of molecules into the CNS of mice.
Download or read book Mouse Models in the Study of Genetic Neurological Disorders written by Brian Popko and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: The number of mouse models that are available for the study of human genetic neurological disorders is large and growing rapidly. Therefore, it was difficult to select the models that were reviewed in this volume. Clearly, there are important models that are not discussed, and perhaps a volume twice this size would have been more appropriate. Moreover, the pace at which new models are being developed and analyzed is rapid. As this volume goes to press, I am sure that additional mouse genes responsible for naturally occurring neurological disorders are being discovered and that many new transgenic and mutant mouse strains are being developed. Therefore, this volume should not be viewed as a comprehensive compendium, but rather as an update of work in progress. It is exhilarating to witness the fast pace at which these models are being established as important tools in the study of basic neuroscience and neurological disorders. It will be even more exciting to see their utilization in the development and testing of therapeutic interventions for these diseases. I would like to thank each of the authors who have contributed to this volume for their time and their expertise. I would also like to thank Drs. Timothy Coetzee and Joshua Corbin for their advice in the selection of the topics covered. I am deeply indebted to Dr. Kunihiko Suzuki, who first approached me with the idea for this volume, for his guidance throughout its preparation.
Download or read book Cellular and molecular mechanisms of motor neuron death in amyotrophic lateral sclerosis written by Ricardo Tapia and published by Frontiers Media SA. This book was released on 2015-02-11 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: Amyotrophic lateral sclerosis (ALS), which was described since 1869 by Jean Martin Charcot, is a devastating neurodegenerative disease characterized by the selective and progressive loss of upper and lower motor neurons of the cerebral cortex, brainstem and the spinal cord. The cognitive process is not affected and is not merely the result of aging because may occur at young ages. The only known cause of the disease is associated with genetic mutations, mainly in the gene encoding superoxide dismutase 1 (familial ALS), whereas there is no known cause of the sporadic form of ALS (SALS), which comprises >90% of cases. Both ALS types develop similar histopathological and clinical characteristics, and there is no treatment or prevention of the disease. Because effective treatments for ALS, as for other neurodegenerative diseases, can only result from the knowledge of their cellular and molecular pathophysiological mechanisms, research on such mechanisms is essential. Although progress in neurochemical, physiological and clinical investigations in the last decades has identified several mechanisms that seem to be involved in the cell death process, such as glutamate-mediated excitotoxicity, alterations of inhibitory circuits, inflammatory events, axonal transport deficits, oxidative stress, mitochondrial dysfunction and energy failure, the understanding of the origin and temporal progress of the disease is still incomplete and insufficient. Clearly, there is a need of further experimental models and approaches to discern the importance of such mechanisms and to discover the factors that determine the selective death of motor neurons characteristic of ALS, in contrast to other neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Whereas studies in vitro in cell cultures, tissue slices or organotypic preparations can give useful information regarding cellular and molecular mechanisms, the experiments in living animal models obviously reflect more closely the situation in the human disease, provided that the symptoms and their development during time mimics as close as possible those of the human disease. It is necessary to correlate the experimental findings in vitro with those in vivo, as well as those obtained in genetic models with those in non-genetic models, aiming at designing and testing therapeutic strategies based on the results obtained.
Download or read book Neurodegenerative Disorders Loss of Function Through Gain of Function written by K. Beyreuther and published by Springer Science & Business Media. This book was released on 2001-03-13 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt: The main message from this book is that the different protein aggregation processes may all be amenable to a small number of intervention steps based on a common theme of the modulation of production, turnover and deposition of the corresponding disease gene products. The next few years will prove critical in evaluation the possibilities of rational therapeutic strategies towards regaining the loss of function through the amelioration of the abnormal gain of function.
Download or read book Animal Models for Neurodegenerative Disease written by Jesús Avila and published by Royal Society of Chemistry. This book was released on 2011 with total page 307 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, medical developments have resulted in an increase in human life expectancy. The editors have extensive knowledge and experience in this field and the book is aimed at undergraduates, postgraduates, and academics. The chapters cover Alzheimer's disease, Parkinson's disease, Huntington's, and other neurodegenerative disorders.
Download or read book Multifaceted Genes in Amyotrophic Lateral Sclerosis Frontotemporal Dementia written by Henry Houlden and published by Frontiers Media SA. This book was released on 2021-06-28 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Molecular and Cellular Basis of Neurodegenerative Diseases written by Michael S. Wolfe and published by Academic Press. This book was released on 2018-03-29 with total page 561 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer’s, Parkinson’s, frontotemporal dementia, ALS, Huntington’s, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration Details features, advantages and limitations of animal models, as well as prospects for therapeutic development Authored by internationally recognized leaders in the field Includes illustrations that help clarify and consolidate complex concepts
Download or read book Molecular Studies on the Pathology of Alzheimer s Disease with Particular Emphasis on Transgenic Mouse Models written by Oliver Wirths and published by . This book was released on 2002 with total page 113 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Amyotrophic Lateral Sclerosis written by Martin Henrik Maurer and published by IntechOpen. This book was released on 2012-01-20 with total page 740 pages. Available in PDF, EPUB and Kindle. Book excerpt: Though considerable amount of research, both pre-clinical and clinical, has been conducted during recent years, Amyotrophic Lateral Sclerosis (ALS) remains one of the mysterious diseases of the 21st century. Great efforts have been made to develop pathophysiological models and to clarify the underlying pathology, and with novel instruments in genetics and transgenic techniques, the aim for finding a durable cure comes into scope. On the other hand, most pharmacological trials failed to show a benefit for ALS patients. In this book, the reader will find a compilation of state-of-the-art reviews about the etiology, epidemiology, and pathophysiology of ALS, the molecular basis of disease progression and clinical manifestations, the genetics familial ALS, as well as novel diagnostic criteria in the field of electrophysiology. An overview over all relevant pharmacological trials in ALS patients is also included, while the book concludes with a discussion on current advances and future trends in ALS research.
Download or read book Molecular Mechanisms of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia written by Yulong Sun and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in modern medicine in the past century have dramatically improved the average life expectancy in the western world. Unfortunately, the molecular mechanisms that maintain the integrity of proteins in the body appear to be unable to keep pace. This has led to a growing prevalence of late-onset diseases involving abnormal accumulation of proteins, especially in the last century. The increase in occurrence of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and transmissible spongiform encephalopathies such as prion disease, has become a great burden to the healthcare system. All of these diseases are currently incurable and fatal, but they share the common hallmark of misfolding and aggregation of proteins within the effected neurons. The discovery and characterization of such proteins have often led to the identification of potential targets for treatment and drug design. In the case of ALS, progressive death of upper and lower motor neurons leads to full-body paralysis, and patient death from respiratory failure. The cause of ALS is currently unknown, but remarkably, regardless of the type of ALS (familial or sporadic), the RNA binding protein, TDP-43, is found in 97% of cases as neuronal inclusions, suggesting a mechanistic role in disease pathogenesis. In this thesis, several techniques are used to enable detailed biophysical characterization the TDP-43 aggregation process in solution and in model membranless organelles. Equilibrium turbidity measurements of the protein under aggregating conditions and the inhibitory effects of native-state stabilizing oligonucleotides on aggregation are presented. The modulatory effects of physiological concentrations of electrolytes on TDP-43 aggregation and their implications are also discussed. A novel technique called spatially targeted optical microproteomics (STOMP) is presented as a method to interrogate the proteomic contents of small cellular features in mammalian tissue in hope of identifying common proteins in neuronal inclusions and stress granules. Although the STOMP technique still requires refinement, the biophysical studies on TDP-43 presented here begin to unravel the complex and largely unknown etiology of what is currently a devastating and incurable disease.
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 Investigation of molecular pathogenesis of amyotrophic lateral sclerosis and mouse models of neurodegeneration written by Ruth Pek Sim Chia and published by . This book was released on 2008 with total page 612 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Human Motor Neuron Diseases written by Lewis P. Rowland and published by Lippincott Williams & Wilkins. This book was released on 1982 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Brain Banking written by and published by Elsevier. This book was released on 2018-02-27 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt: Brain Banking, Volume 150, serves as the only book on the market offering comprehensive coverage of the functional realities of brain banking. It focuses on brain donor recruitment strategies, brain bank networks, ethical issues, brain dissection/tissue processing/tissue dissemination, neuropathological diagnosis, brain donor data, and techniques in brain tissue analysis. In accordance with massive initiatives, such as BRAIN and the EU Human Brain Project, abnormalities and potential therapeutic targets of neurological and psychiatric disorders need to be validated in human brain tissue, thus requiring substantial numbers of well characterized human brains of high tissue quality with neurological and psychiatric diseases. Offers comprehensive coverage of the functional realities of brain banking, with a focus on brain donor recruitment strategies, brain bank networks, ethical issues, and more Serves as a valuable resource for staff in existing brain banks by highlighting best practices Enhances the sharing of expertise between existing banks and highlights a range of techniques applicable to banked tissue for neuroscience researchers Authored by leaders from brain banks around the globe – the broadest, most expert coverage available
Download or read book The Deanna Protocol written by Vincent Tedone and published by . This book was released on 2015-07-10 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The authors are in a life and death struggle against a terrible disease, Amyotrophic Lateral Sclerosis, which is referred to as ALS or Lou Gehrig's disease. If you or a loved one have been diagnosed with ALS, then you need to read this book. The Deanna Protocol® program was discovered by Dr. Tedone, Deanna's father, only after failing, again and again, with everything that he tried. The massage, non-exhausting exercise and core supplements, which are inexpensive and available without prescription from many suppliers. The program works for many ALS patients. It is not a cure, however, it provides a better quality of life and has been shown in ALS mice to extend life and improve motor skills. The rate of progression of ALS symptoms reported in ALSFRS scores, is markedly reduced in those adhering to the Deanna Protocol® program. There a few side effects reported, and those are manageable for most, if the program is phased in, gradually, over time.
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 Limbic predominant Age related TDP 43 Encephalopathy written by Beller Health and published by Independently Published. This book was released on 2019-05-13 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Book 9 focuses on a new dementia type, LATE, mistaken as Alzheimer's disease until now.LATE stands for Limbic-predominant age-related TDP-43 encephalopathy, the protein buildup responsible for this dementia. This book is organic, like the series, meaning we never consider our books as finished. Science evolves, which is why our books go through continuous updates. Since LATE is a new dementia classification, we expect continuous further information to emerge. Watch Amazon alerts for potential digital updates. We provide free digital copies on all paperback purchases, so everybody receives free updates.
