Timchenko Triple Repeat Diseases of the Nervous Systems

Erscheinungsjahr 2012
ISBN: 978-1-4615-0117-6
Verlag: Springer US
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 516, 121 Seiten, eBook

Reihe: Advances in Experimental Medicine and Biology

World of Unstable Mutations The book "Triplet Repeat Diseases of the Nervous System" overviews the lat est data on several disorders associated with unstable mutations. This field of re search is progressing extremely fast. The number of polymorphic mutations and diseases caused by these mutations is increasing almost every month. There is a strong interest to molecular bases of triplet repeat disorders. This is explained by growing necessity to develop molecular approaches for cure of these diseases. There fore, the authors of this book describe unstable mutations with the emphasis on molecular pathology. Broad discussion is presented on how polymorphic expan sions cause cell dysfunction. o The first chapter of the book focuses on the molecular pathological pro cesses that originate "unstable" mutations. The authors review several avail able models by which normal "stable" region of DNA become pathogenic and discuss possible mechanisms causing DNA instability. o The other chapters of the book describe inherited diseases associated with different types of unstable mutations. Based on the location of mutation in the disease gene, polymorphic expansions of the nervous system can be divided into two major groups. First group includes disorders with unstable expansions within the open reading frame of the gene such as Spinocer ebellar Ataxias caused by polyglutamine expansions. The second group in cludes diseases caused by expansions situated within the untranslated re gions of the gene.

Zielgruppe

Research

Autoren/Hrsg.

Timchenko, Lubov T.

Inhaltsverzeichnis

1. Molecular Mechanisms of TRS Instability.- Secondary DNA Structures as a Source of TRS Instability.- Summary.- 2. Myotonic Dystrophy: Discussion of Molecular Basis.- DM1 Mutation is an Expansion of CTG Trinucleotide Repeats.- Mouse Models of Unstable DNA.- Molecular Pathogenesis of DM1.- Deficiency of SIX5 in DM1.- Alterations of RNA Metabolism in DM1.- CUGBP1 Targets.- Other Members of CUGBP1 Family.- Conclusions.- 3. Spinocerebellar Ataxias Caused By Polyglutamine Expansions.- Polyglutamine Expansions as Major Mutations in ADCA.- Age at Onset.- Clinical Presentation in Patients.- Neuropathological Lesions.- Factors Influencing Clinical Variability.- Physiopathology of Spinocerebellar Ataxias Caused by Polyglutamine Expansions.- Conclusions.- Towards Therapy.- 4. Spinocerebellar Ataxia Type 10: A Disease Caused by a Large ATTCT Repeat Expansion.- Clinical Features.- Identification of the SCA10 Mutation.- Prospects of Research.- 5. The Molecular Basis of Friedreich Ataxia.- Gene Structure and Expression.- Point Mutations.- Frataxin Structure and Function.- Current Hypotheses for the Pathogenesis of Friedrich Ataxia.- Approaches for Treatment.