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Axonal Transport Of The Parkinsons Disease Protein Alpha Synuclein
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Book Synopsis Axonal Transport of the Parkinson's Disease Protein Alpha-Synuclein by : Eric Anderson
Download or read book Axonal Transport of the Parkinson's Disease Protein Alpha-Synuclein written by Eric Anderson and published by . This book was released on 2017 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: The intracellular transport of protein complexes, membrane-bound vesicles, organelles, and RNA along microtubule (MT) tracks to the axonal terminal is crucial for neuronal survival and function. In neurodegenerative disorders, such as Parkinson's disease (PD), defects in the axonal transport pathway are suggested to be major contributors to neurodegeneration. a-syn (a-syn) is a small acid protein that is actively transported from the cell body to the axonal terminal and is the main constituent of Lewy bodies (LB), abnormal deposits of protein in the brain in PD. In my dissertation research, I have focused on the mechanism of a-syn transport in axons. The effects of familial PD (fPD) mutations on the transport of a-syn and synaptic proteins were also studied using Drosophila melanogaster (fruit flies) as a model organism. I have found that the aggregate-prone non-amyloidal component (NAC) region in a-syn was required for the dimerization and membrane binding for a-syn during its transport to the axonal terminal. Deletion of a-syn NAC region (delNAC) resulted in an increase in its accumulation within cell bodies located in the brain, decreased its entry into axons, and its transport to the axonal terminal. This decrease in the transport of delNAC to the axonal terminal is due to decreased membrane interaction of a-syn. I have also demonstrated that increased levels of a-syn (3-fold increase mimicking gene triplication in PD or fPD mutation (Alanine53Threoine, A53T)) accumulation in axons disrupt the axonal transport of synaptic proteins, resulting in synaptic morphological defects and locomotion behavior defects. This accumulation of Îł-syn in axons is likely due to dimerization of Îł-syn through the NAC region, possibly on membranes. Therefore, this part of the study revealed an important role for the NAC region in mediating a-syn dimerization on membranes for a-syn transport to the axonal terminal. The second part of the study focused on the effects of a-syn on Rab3 motility. The Rab3 protein, a neuronal guanosine triphosphate (GTP)-binding protein, has been proposed to present together with a-syn on vesicles and has a similar function in regulating synaptic vesicle trafficking. In vivo live image analysis showed disruption of Rab3 motility with excess or fPD mutant a-syn, and mutant Rab3 disrupted the transport of a-syn-containing vesicle to the axonal terminal. Thus, this study highlights, for the first time, a potential interaction between Rab3 and a-syn in the axonal transport pathway. Collectively, these studies provided new insights into our understanding of the a-syn protein in the axonal transport pathway. Alteration in the axonal transport pathway can have important implications in PD, thus, elucidating the mechanism of a-syn protein transport and Îł-syn-mediated disruption of the axonal transport pathway is critical to our overall understanding of the contribution of this pathway to the disease progression.
Book Synopsis The Protein Alpha-Synuclein: Its Normal Role (in Neurons) and its Role in Disease by : Fredric P. Manfredsson
Download or read book The Protein Alpha-Synuclein: Its Normal Role (in Neurons) and its Role in Disease written by Fredric P. Manfredsson and published by Frontiers Media SA. This book was released on 2020-03-25 with total page 151 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Accumulation of [alpha]-Synuclein Impairs Trafficking and Processing of Amyloid Precursor Protein in a Mouse Model of Parkinson's Disease by : Savannah YT Fang
Download or read book Accumulation of [alpha]-Synuclein Impairs Trafficking and Processing of Amyloid Precursor Protein in a Mouse Model of Parkinson's Disease written by Savannah YT Fang and published by . This book was released on 2020 with total page 49 pages. Available in PDF, EPUB and Kindle. Book excerpt: Parkinson's Disease (PD) is the second most common neurodegenerative disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra of the brain possibly due to the accumulation of [alpha]-synuclein (ASYN). Mutations or triplication of the ASYN gene (SNCA) contribute to synucleinopathies including PD, but studies have also noted that a significant portion of PD patients develop Alzheimer's Disease (AD) like dementia. Therefore, we hypothesized that excessive accumulation of ASYN may also impact the trafficking and processing of the amyloid precursor protein (APP), initiating the pathogenesis of AD. To test our hypothesis, we used a transgenic mouse model of PD that over-expresses a green fluorescent protein fused human ASYN (GFP-hASYN) transgene. Our findings suggest that the over-expression of GFP-hASYN in mouse neurons i.e. PD neurons impaired axonal trafficking and processing of APP. Furthermore, APP carboxyl terminal fragment (APP CTF) levels were significantly higher in GFP-hASYN+ positive PD neurons than in GFP-hASYN- neurons, suggesting impairment in downstream processes. Interestingly, in ASYN knockout (SynKO) neurons, APP trafficking and processing was largely unaffected as compared to wildtype (WT) neurons'. Based on these observations, we speculate that selective impairment of trafficking and processing of APP by ASYN may give rise to toxic CTFs, which may contribute to blockages, leading to endosomal enlargement, axonal transport impairment and eventually neuronal atrophy. This study provides an important molecular mechanism by which excessive accumulation of ASYN could potentially be linked to cellular events that lead to AD pathogenesis in addition to its role in inducing neurotoxicity in PD pathology.
Book Synopsis A new Perspective on Parkinson's disease: exploring the involvement of intestine and vagus lysates in α-synucleinopathy propagation by : Rahat Ullah
Download or read book A new Perspective on Parkinson's disease: exploring the involvement of intestine and vagus lysates in α-synucleinopathy propagation written by Rahat Ullah and published by OAE Publishing Inc.. This book was released on 2023-03-29 with total page 5 pages. Available in PDF, EPUB and Kindle. Book excerpt: In Parkinson's disease (PD), the accumulation of misfolded α-synuclein (α-syn) in the brain is a major characteristic of the pathology. α-Syn formation and aggregation may originate in the enteric nervous system and pathologic α-syn can be transmitted to the central nervous system via the vagus nerve. In this commentary, we summarize the findings of Yang et al.[1] in which they report on the ability of a Parkinson’s disease patient's intestinal and vagus lysates containing pathologic α-syn to template endogenous rat α-syn culminating in the spread of pathologic α-syn, deposition of pathologic α-syn, and neuroinflammation in different brain regions and neurodegeneration of dopamine neurons. These observations are discussed with other studies supporting the significance of the gastrointestinal system in PD pathogenesis and future directions of research are highlighted.
Book Synopsis Dopamine Handbook by : Leslie L. Iversen
Download or read book Dopamine Handbook written by Leslie L. Iversen and published by . This book was released on 2010 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of dopamine in 1957-1958 was one of the seminal events in the development of modern neuroscience, and has been extremely important for the development of modern therapies of neurological and psychiatric disorders. Dopamine has a fundamental role in almost all aspects of behavior: from motor control to mood regulation, cognition and addiction and reward, and dopamine research has been unique within the neurosciences in the way it has bridged basic science and clinical practice. Over the decades research into the role of dopamine in health and disease has been in the forefront of modern neuroscience. The Dopamine Handbook is the first single-volume publication to capture current progress and excitement in this dynamic research field.
Book Synopsis Neuroanatomy and Pathology of Sporadic Parkinson's Disease by : Heiko Braak
Download or read book Neuroanatomy and Pathology of Sporadic Parkinson's Disease written by Heiko Braak and published by Springer. This book was released on 2008-12-03 with total page 119 pages. Available in PDF, EPUB and Kindle. Book excerpt: The synucleinopathy sporadic Parkinson’s disease (sPD) is the second most frequent degenerative disorder of the human nervous system after Alzheimer’s disease. The propensity for developing sPD exists in all ethnic groups worldwide, and the prevalence of the disorder increases considerably with age, thereby imposing an enormous social and economic burden on societies with increased life expectancy. The sPD-associated pathological process is progressive, does not go into remission, and can take decades to reach its culmination if it is not be terminated prematurely by death owing to other causes. Against the background of the normal morphology and anatomy, the authors analyze the pathoanatomy of sPD in the nervous system at various neuropathological stages and summarize the potential functional consequences of the lesions.
Book Synopsis Mitochondria and Endoplasmic Reticulum Dysfunction in Parkinson’s Disease by : Sandeep Kumar Barodia
Download or read book Mitochondria and Endoplasmic Reticulum Dysfunction in Parkinson’s Disease written by Sandeep Kumar Barodia and published by Frontiers Media SA. This book was released on 2020-01-23 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt: Several pathogenic mechanisms are involved in the pathogenesis of Parkinson’s Disease (PD), a neurodegenerative disease characterized by the loss of substantial nigra (SN) dopamine (DA) neurons. Alterations in calcium (Ca2+) homeostasis, cellular proteostasis, axonal transport, mitochondrial function, and neuroinflammation are linked to PD. However, research involving inter-organelle communication and their significance as precise mechanisms underlying neuronal death in PD remain to be elucidated. Evidence showed that perturbations in the mitochondria-endoplasmic reticulum (ER) network play an important role in the pathogenesis of PD. Alterations in the mitochondria-ER interface have been reported in PARK2 knockout mice and patients harboring PARK2 mutations. Enhanced parkin levels maintain mitochondria-ER cross-talk and assure regulated Ca2+ transfer to sustain cell bioenergetics. Several familial PD-related proteins, including Parkin and PINK1, may lead to modifications in the mitochondria-ER signaling. Interestingly, mitochondria-ER tethering suppresses mitophagy and parkin/PINK1-dependent mechanism regulates the destruction of mitochondria-ER contact sites by catalyzing a rapid burst of Mfn2 phospho-ubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane. Mitofusin-mediated ER stress elicited neurodegeneration in Pink1/Parkin models of PD. α-Synuclein, a presynaptic protein, can bind to the ER-mitochondria tethering protein vesicle-associated membrane protein-associated protein B (VAPB) to disrupt Ca2+ homeostasis and mitochondrial ATP production. It has been reported that ER stress and mitochondrial cell death pathways might mediate A53T mutant α-synuclein-induced toxicity. Mitochondria-ER signaling mechanism is poorly characterized in neurons and its association in neuronal pathophysiology remains uncertain. The presence of mitochondria-ER contacts in neurons, preferentially at synapses, suggests a potential role in regulating synaptic activity. Alterations in mitochondria-ER associations are expected to be potentially detrimental to neurons, especially to SN DA neurons. Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and associated mitochondrial dysfunction in different PD models. In addition, a dibenzoylmethane derivative protects DA neurons against ER stress. Thus, mitochondria-ER signaling may represent a possible upstream drug target as potential therapeutic strategy for PD. In this Research Topic, we bring together knowledge that emphasizes the importance of mitochondria-ER communication and its impact to further dissect the pathogenic mechanisms in PD.
Book Synopsis Etiology of Parkinson's Disease by : Jonas H. Ellenberg
Download or read book Etiology of Parkinson's Disease written by Jonas H. Ellenberg and published by CRC Press. This book was released on 1995-03-01 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.
Book Synopsis Neurodegenerative Diseases by : Shamim I. Ahmad
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.
Book Synopsis Investigating Mechanisms Involved in [alpha]-synuclein Axonal Transport by : Josephine Elizabeth Hill
Download or read book Investigating Mechanisms Involved in [alpha]-synuclein Axonal Transport written by Josephine Elizabeth Hill and published by . This book was released on 2004 with total page 550 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Leucine-Rich Repeat Kinase 2 (LRRK2) by : Hardy J. Rideout
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.
Book Synopsis The Enteric Nervous System by : John Barton Furness
Download or read book The Enteric Nervous System written by John Barton Furness and published by . This book was released on 1987 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Neuronal Cell Death by : Laura Lossi
Download or read book Neuronal Cell Death written by Laura Lossi and published by Humana Press. This book was released on 2014-11-28 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume represents a valuable and readily reproducible collection of established and emerging techniques for neuronal cell death research. Conveniently divided into four parts, sections cover a series of techniques for the molecular, structural, functional and genomic characterization of dying neurons, a number of protocols that are of primary interest in neuropathology and in experimental neuropathology, a series of gene engineering techniques to obtain and manipulate neuronal stem cells and progenitors, to prepare HSV-1 vectors for the gene therapy, and to CNS transplantation of bone marrow stem cells, and finally, some very interesting protocols for the study of cell death in non-mammalian models. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neuronal Cell Death: Methods and Protocols seeks to serve a large audience of scientists that are currently active in the field or are willing to enter such an exciting and still expanding area of neurobiology.
Book Synopsis Mitochondrial Dysfunction by : Lawrence H. Lash
Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
Book Synopsis Alpha-synuclein by : Howard C. Kanowitz
Download or read book Alpha-synuclein written by Howard C. Kanowitz and published by Nova Science Pub Incorporated. This book was released on 2013-01-01 with total page 61 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alpha-synuclein is a synuclein protein of unknown function primarily found in neural tissue, making up as much as 1% of all proteins in the cytosol. It is predominantly expressed in the neocortex, hippocampus, substantia nigra, thalamus, and cerebellum. In this book, the authors discuss the functional mechanisms, structure and role in Parkinson's disease of alpha-synuclein. Topics include α-synuclein accumulation in Parkinsons disease and multiple system atrophy; α-synuclein metabolism and aggregation in the pathogenesis of Parkinsons disease; and the potential role of α-synuclein dysregulation in Parkinsons disease pathology.
Book Synopsis Proteopathic Seeds and Neurodegenerative Diseases by : Mathias Jucker
Download or read book Proteopathic Seeds and Neurodegenerative Diseases written by Mathias Jucker and published by Springer Science & Business Media. This book was released on 2013-03-27 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: The misfolding and aggregation of specific proteins is an early and obligatory event in many of the age-related neurodegenerative diseases of humans. The initial cause of this pathogenic cascade and the means whereby disease spreads through the nervous system, remain uncertain. A recent surge of research, first instigated by pathologic similarities between prion disease and Alzheimer’s disease, increasingly implicates the conversion of disease-specific proteins into an aggregate-prone b-sheet-rich state as the prime mover of the neurodegenerative process. This prion-like corruptive protein templating or seeding now characterizes such clinically and etiologically diverse neurological disorders as Alzheimer ́s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration. Understanding the misfolding, aggregation, trafficking and pathogenicity of the affected proteins could therefore reveal universal pathomechanistic principles for some of the most devastating and intractable human brain disorders. It is time to accept that the prion concept is no longer confined to prionoses but is a promising concept for the understanding and treatment of a remarkable variety of diseases that afflict primarily our aging society.
Book Synopsis Alpha-synuclein-associated Alterations at the Synapse in Models of Parkinson's Disease by : Patrícia Pires dos Santos
Download or read book Alpha-synuclein-associated Alterations at the Synapse in Models of Parkinson's Disease written by Patrícia Pires dos Santos and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Parkinson's disease (PD) is one of the most common neurodegenerative disorders that is characterized by the typical motor features, and also by a multiplicity of non-motor symptoms. The main pathological hallmarks of PD are a progressive, and profound, loss of dopaminergic neurons in the substantia nigra, as well as the accumulation of protein inclusions rich in the protein alpha-synuclein (aSyn). Yet, the exact molecular mechanisms linking aSyn to PD remain unknown. Despite the fact that aSyn is involved in producing synaptic vesicles (SVs) and their transport, in SNARE complex assembly, a...
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