Modulation of RNA-dependent Interactions in Stress Granules Prevents Persistent TPD-43 Accumulation in ALS/FTD PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Modulation of RNA-dependent Interactions in Stress Granules Prevents Persistent TPD-43 Accumulation in ALS/FTD PDF full book. Access full book title Modulation of RNA-dependent Interactions in Stress Granules Prevents Persistent TPD-43 Accumulation in ALS/FTD by Mark Yang Fang. Download full books in PDF and EPUB format.
Author: Mark Yang Fang
Publisher:
ISBN:
Category :
Languages : en
Pages : 163
Get Book Here
Book Description
Stress granules (SG) form during cellular stress and have been linked to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Strategies to modulate SGs have the potential to yield insights into their role in pathophysiology. We performed a high-content screen to identify small molecules that alter SG properties in proliferative cells and iPSC-derived motor neurons (iPS-MNs). One major class of hit compounds are nucleic acid intercalating molecules that disrupt recruitment of ALS-associated RNA-binding proteins (RBPs), such as TDP-43 and FUS/TLS, into SGs and reduce accumulation of cytoplasmic TDP-43 in iPS-MNs from ALS patients. These findings corroborate our biochemical results indicating that SGs accumulate ALS-associated RBPs in their shells in an RNA-dependent manner. Thus, SGs contribute to persistent accumulation of TDP-43, and nucleic acid intercalating compounds represent a promising new therapeutic approach for treating ALS/FTD.
Author: Mark Yang Fang
Publisher:
ISBN:
Category :
Languages : en
Pages : 163
Get Book Here
Book Description
Stress granules (SG) form during cellular stress and have been linked to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). Strategies to modulate SGs have the potential to yield insights into their role in pathophysiology. We performed a high-content screen to identify small molecules that alter SG properties in proliferative cells and iPSC-derived motor neurons (iPS-MNs). One major class of hit compounds are nucleic acid intercalating molecules that disrupt recruitment of ALS-associated RNA-binding proteins (RBPs), such as TDP-43 and FUS/TLS, into SGs and reduce accumulation of cytoplasmic TDP-43 in iPS-MNs from ALS patients. These findings corroborate our biochemical results indicating that SGs accumulate ALS-associated RBPs in their shells in an RNA-dependent manner. Thus, SGs contribute to persistent accumulation of TDP-43, and nucleic acid intercalating compounds represent a promising new therapeutic approach for treating ALS/FTD.
Author: Annakaisa Haapasalo
Publisher: Frontiers Media SA
ISBN: 2889717771
Category : Science
Languages : en
Pages : 188
Get Book Here
Book Description
Author: Akihiko Takashima
Publisher: Springer Nature
ISBN: 9813293586
Category : Medical
Languages : en
Pages : 416
Get Book Here
Book Description
This book presents essential studies and cutting-edge research results on tau, which is attracting increasing interest as a target for the treatment of Alzheimer's disease. Tau is well known as a microtubule-associated protein that is predominantly localized in the axons of neurons. In various forms of brain disease, neuronal loss occurs, with deposition of hyperphosphorylated tau in the remaining neurons. Important questions remain regarding the way in which tau forms hyperphosphorylated and fibrillar deposits in neurons, and whether tau aggregation represents the toxic pathway leading to neuronal death. With the help of new technologies, researchers are now solving these long-standing questions. In this book, readers will find the latest expert knowledge on all aspects of tau biology, including the structure and role of the tau molecule, tau localization and function, the pathology, drivers, and markers of tauopathies, tau aggregation, and treatments targeting tau. Tau Biology will be an invaluable source of information and fresh ideas for those involved in the development of more effective therapies and for all who seek a better understanding of the biology of the aging brain.
Author: Rita Sattler
Publisher: Springer
ISBN: 331989689X
Category : Medical
Languages : en
Pages : 321
Get Book Here
Book Description
It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Author: Detlev Boison
Publisher: Frontiers Media SA
ISBN: 2889710637
Category : Science
Languages : en
Pages : 160
Get Book Here
Book Description
Author: Lawrence H. Lash
Publisher: Elsevier
ISBN: 1483218619
Category : Science
Languages : en
Pages : 527
Get Book Here
Book Description
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.
Author: Ron Milo
Publisher: Garland Science
ISBN: 1317230698
Category : Science
Languages : en
Pages : 400
Get Book Here
Book Description
A Top 25 CHOICE 2016 Title, and recipient of the CHOICE Outstanding Academic Title (OAT) Award. How much energy is released in ATP hydrolysis? How many mRNAs are in a cell? How genetically similar are two random people? What is faster, transcription or translation?Cell Biology by the Numbers explores these questions and dozens of others provid
Author: Marlene Oeffinger
Publisher: Springer Nature
ISBN: 3030314340
Category : Science
Languages : en
Pages : 318
Get Book Here
Book Description
The book provides an overview on the different aspects of gene regulation from an mRNA centric viewpoint, including how mRNA is assembled and self-assembles in a complex consisting of RNA and proteins, and how its ability to be translated at the right time and space depends on many processes acting on the mRNAs, leading to a properly folded complex. This book shows how new technologies have led to a better understanding of these processes and their connected diseases.The book is written for scientists in fundamental and applied biomedical research working on different aspects of gene regulation. It is also targeted to an audience that is not implicated in these fields directly, but wants to gain a better understanding of mRNA biology.
Author: Dennis Dickson
Publisher: John Wiley & Sons
ISBN: 1444341235
Category : Medical
Languages : en
Pages : 497
Get Book Here
Book Description
Most textbooks on neurodegenerative disorders have used a classification scheme based upon either clinical syndromes or anatomical distribution of the pathology. In contrast, this book looks to the future and uses a classification based upon molecular mechanisms, rather than clinical or anatomical boundaries. Major advances in molecular genetics and the application of biochemical and immunocytochemical techniques to neurodegenerative disorders have generated this new approach. Throughout most of the current volume, diseases are clustered according to the proteins that accumulate within cells (e.g. tau, α-synuclein and TDP-43) and in the extracellular compartments (e.g. β-amyloid and prion proteins) or according to a shared pathogenetic mechanism, such as trinucleotide repeats, that are a feature of specific genetic disorders. Chapters throughout the book conform to a standard lay-out for ease of access by the reader and are written by a panel of International Experts Since the first edition of this book, major advances have been made in the discovery of common molecular mechanisms between many neurodegenerative diseases most notably in the frontotemporal lobar degenerations (FTLD) and motor neuron disease or amyotrophic lateral sclerosis. This book will be essential reading for clinicians, neuropathologists and basic neuroscientists who require the firm up-to-date knowledge of mechanisms, diagnostic pathology and genetics of Neurodegenerative diseases that is required for progress in therapy and management.
Author: Philippe Jeanteur
Publisher: Springer Science & Business Media
ISBN: 3540344497
Category : Science
Languages : en
Pages : 265
Get Book Here
Book Description
Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.
