Polyglutamine Disorders
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Polyglutamine Disorders
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Author : Clévio Nóbrega
language : en
Publisher: Springer
Release Date : 2018-02-09
Polyglutamine Disorders written by Clévio Nóbrega and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-02-09 with Medical categories.
This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies’ development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington’s disease (HD); spinal–bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression.
Developing Genetic Therapies For Polyglutamine Disorders
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Author :
language : en
Publisher:
Release Date : 2015
Developing Genetic Therapies For Polyglutamine Disorders written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with categories.
Towards Understanding The Pathogenesis Of Polyglutamine Disorders
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Author : Katrin S. Lindenberg
language : en
Publisher:
Release Date : 2002
Towards Understanding The Pathogenesis Of Polyglutamine Disorders written by Katrin S. Lindenberg and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with categories.
The Role Of Polyglutamine Aggregate Cytotoxicity In Huntington S Disease
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Author :
language : en
Publisher:
Release Date : 2003
The Role Of Polyglutamine Aggregate Cytotoxicity In Huntington S Disease written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2003 with categories.
Polyglutamine diseases refer to a group of neurodegenerative diseases, including Huntington's disease (HD), that share the same mutational basis: expansion of a CAG repeat coding sequence that encodes for a polyglutamine repeat in the respective proteins. Neuronal intranuclear inclusions (NII) formed by the aggregation of the expanded polyglutamine proteins is a hallmark of polyglutamine diseases. However, it is still under debate whether the polyglutamine aggregates are toxic to the cells, and if so, which aggregated forms are the toxic species. While important data has been provided by the existing transfected cell and transgenic animal models, technical aspects have limited our ability to rigorously interpret this data in terms of molecular and cellular mechanism. A number of comprehensive studies on in vitro polyglutamine aggregation kinetics, and features of the aggregates produced in vitro, provided the foundation to directly address the question of the cytotoxicity of polyglutamine aggregates. In the present study, we designed a new cell model by directly introducing in vitro synthesized polyglutamine aggregates into mammalian cells, both PC-12 and Cos-7, to study the cytotoxicity of different forms of aggregates. We found that cell viability was largely unaffected when polyglutamine aggregates are localized to the cytoplasm; aggregates of polyglutamine peptides containing a nuclear localization signal, however, are localized to nuclei and lead to dramatic cell death. This cytotoxicity is polyglutamine-sequence-specific. We also found that a short polyglutamine peptide (Q20), once aggregated and delivered to the cell nucleus, seems to be equally cytotoxic. Further studies suggest that the mechanism of cell death in this novel model system seems to be apoptotic. Our results support a direct role for polyglutamine aggregates in cytotoxicity and are consistent with a recruitment-sequestration disease mechanism. This is further supported by studies, also described here, in which a polyglutamine aggregation elongation inhibitor protects against cell death induced by nuclear polyglutamine aggregates.
Transcriptional Co Activator Dysfunction In Polyglutamine Disease
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Author : Alexander McCampbell
language : en
Publisher:
Release Date : 2001
Transcriptional Co Activator Dysfunction In Polyglutamine Disease written by Alexander McCampbell and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2001 with categories.
Biomarkers Identification And Disease Modeling Using Multimodal Neuroimaging Approaches In Polyglutamine Diseases
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Author : Isaac Mawusi Adanyeguh
language : en
Publisher:
Release Date : 2017
Biomarkers Identification And Disease Modeling Using Multimodal Neuroimaging Approaches In Polyglutamine Diseases written by Isaac Mawusi Adanyeguh and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
Mutations in different gene loci that lead to the encoding of the unstable and expanded glutamine-encoding cytosine-adenine-guanine (CAG) repeats results in the group of diseases known as the polyglutamine diseases. This project focuses on the most common forms which are Huntington disease (HD) and spinocerebellar ataxia (SCA) types 1, 2, 3 and 7. These are autosomal dominant diseases responsible for severe movement disorders and are thought to share common pathophysiological pathways with a major emphasis on metabolic dysfunction. The availability of genetic testing and their predominantly adult onset opens a window for therapeutic intervention before symptoms onset. However, current clinical scales are not sensitive and cannot effectively be used to evaluate individuals at the presymptomatic stage of the diseases. This prompts the need for biomarkers that are sensitive to macroscopic and microscopic changes that may occur prior to disease onset. Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques present non-invasive approaches to extract pertinent information that otherwise would not be possible with clinical scales. In this work therefore, we present a combination of different MRI and MRS techniques to identify robust biomarkers in HD and SCA. We also present therapeutic approaches that hold promise in HD. Likewise, we show that imaging biomarkers have higher effect sizes than clinical scales. Finally, we combine multimodal data - volumetry, MRS, metabolomics and lipidomic - from SCA into a model that best explains the pathology.
Molecular Mechanisms Of Polyglutamine Pathology And Lessons Learned From Huntington S Disease
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Author : Nagehan Ersoy Tunalı
language : en
Publisher:
Release Date : 2019
Molecular Mechanisms Of Polyglutamine Pathology And Lessons Learned From Huntington S Disease written by Nagehan Ersoy Tunalı and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with Electronic books categories.
Identification of polymorphic repeating units on DNA as a cause of many neurological disorders has introduced a new concept in molecular biology: Dynamic mutations. Many of the identified dynamic mutations involve expansion of trinucleotide repeats within disease genes. Nine neurodegenerative disorders are currently known to be caused by expanding CAG trinucleotide repeats. These are Huntington,Äôs Disease (HD), Dentato-Rubral Pallidoluysian Atrophy (DRPLA), Spinal and Bulbar Muscular Atrophy (SBMA), and Spinocerebellar Ataxia (SCA) Type 1, 2, 3, 6, 7 and 17. All are inherited in an autosomal dominant fashion except for SBMA, which is X-linked recessive. In all polyQ diseases, the disease mutation involves an increase in the number of CAG repeats within the coding regions of the respective genes. Since CAG triplets encode glutamine in the proteins, diseases caused by CAG repeat expansions are known as ,ÄúPolyglutamine (polyQ) Diseases,Äù. PolyQ diseases share certain clinical, neuropathological and molecular findings. The most widely studied polyQ disease is HD. In HD and other polyQ diseases, conformational change in the mutant protein causes abnormal folding and proteolysis of the protein, leading to the formation of a toxic polyQ fragment, which aggregates and causes neuronal dysfunction and selective neuronal death in the brain.
Calpains In The Molecular Pathogenesis Of Polyglutamine Disorders And Their Potential As A Therapeutic Target
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Author : Jonasz Jeremiasz Weber
language : en
Publisher:
Release Date : 2018
Calpains In The Molecular Pathogenesis Of Polyglutamine Disorders And Their Potential As A Therapeutic Target written by Jonasz Jeremiasz Weber and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Polyglutamine Diseases
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Author :
language : en
Publisher:
Release Date : 2007
Polyglutamine Diseases written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.
Protein Quality Control Pathways In Polyglutamine Diseases
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Author : María Alexandra Rujano
language : en
Publisher:
Release Date : 2007
Protein Quality Control Pathways In Polyglutamine Diseases written by María Alexandra Rujano and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.