Polyglutamine Diseases-Understanding the Mechanism of Pathogenesis
TLDR
These reviews will focus primarily on cellular processes that are affected in Polyglutamine disorders, and discover several modifiers for these fatal diseases.Abstract:
Protein misfolding has been implicated in a large number of diseases, which are now grouped under the name of Protein conformational disorders (PCDs). Few examples of diseases that fall in this group are Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. All these disorders are characterized by sets of protein that misfold and aggregate in specific tissues. In order to identify and develop possible routes of therapeutic strategies, scientists have discovered several modifiers for these fatal diseases. These modifiers, primarily identified using models systems, include heat shock proteins, components of UPS pathway and autophagy, transcription factors, detoxifying enzymes, several RNA binding proteins, and RNA species, among other examples. These reviews will focus primarily on cellular processes that are affected in Polyglutamine disorders.read more
Citations
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Journal ArticleDOI
Polyglutamine ataxias: From Clinical and Molecular Features to Current Therapeutic Strategies
TL;DR: Several pathogenic pathways have been implicated in polyglutamine spinocerebellar ataxia diseases, such as the hallmark feature of neuronal nuclear inclusions, protein misfolding and aggregation, as well as transcriptional dysregulation.
Book ChapterDOI
Mystery of Expansion: DNA Metabolism and Unstable Repeats.
TL;DR: The mammalian genome mostly contains repeated sequences, and their instability, particularly the propensity to change the repeat unit number, is responsible for 36 well-known neurodegenerative human disorders.
References
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Journal Article
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Manish A. Shah,Nicole A. Datson,Lakshmi Srinidhi,Vincent P. Stanton,Marcy E. MacDonald,Marc W. Allard,S. Youngman,Anna-Maria Frischauf,Richard Mott,KM Draths,Günther Zehetner,C. O’Donovan,Thomas J. Fielder,Bruce G. Jenkins,Manju Swaroop,Sherryl A.M. Taylor,Lynn Doucette-Stamm,Heather MacFarlane,Scott A. Strobel,H. E. McFarlane,Alan Buckler,Nicolet Groot,Holger Hummerich,Deanna M. Church,M. A. Anderson,Marianne James,Glenn Barnes,M. Christine,Francis S. Collins,Mabel P. Duyao,Peter B. Dervan,Gillian P. Bates,T Holloway,Peter S. Harper,TW Mcdonald,M North,K Blanchard,John J. Wasmuth,D. Shaw,Hans Lehrach,Danilo A. Tagle,Annemarie Poustka,David E. Housman,T. Huntington,Zdenek Sedlacek,Laura Riba,Susan F. Kirby,Carol Lin,Richard H. Myers,Leslie M. Thompson,Russell G. Snell,Michael Conlon O'Donovan,K Gillespie,Rita Shiang,Nancy S. Wexler,Christine Ambrose,J. F. Gusella,Sarah Baxendale,N. Groat,John Valdes +59 more
TL;DR: The Huntington's disease mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype.
Journal ArticleDOI
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
Marian DiFiglia,Ellen Sapp,Kathryn Chase,Stephen W. Davies,Gillian P. Bates,J. P. Vonsattel,Neil Aronin +6 more
TL;DR: An NH2-terminal fragment of mutant huntingtin was localized to neuronal intranuclear inclusions and dystrophic neurites in the HD cortex and striatum, and polyglutamine length influenced the extent of huntingtin accumulation in these structures.
Journal ArticleDOI
Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy.
TL;DR: It is concluded that enlargement of the CAG repeat in the androgen receptor gene is probably the cause of X-LINKED spinal and bulbar muscular atrophy.
Journal ArticleDOI
Neuropathological classification of Huntington's disease.
Jean-Paul Vonsattel,Richard H. Myers,Thomas J. Stevens,Robert J. Ferrante,Edward D. Bird,Edward P. Richardson +5 more
TL;DR: These studies indicate that analyses of the caudate nucleus in grade 4 would reflect mainly its astrocytic composition with a component of remote neurons projecting to the striatum, which would reflect early cellular and biochemical changes in HD.
Journal ArticleDOI
Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the hd mutation
Stephen W. Davies,Mark Turmaine,Barbara A. Cozens,Marian DiFiglia,Alan H. Sharp,Christopher A. Ross,Eberhard Scherzinger,Erich E. Wanker,Laura Mangiarini,Gillian P. Bates +9 more
TL;DR: In this paper, the authors observed that mice transgenic for exon 1 of the human HD gene carrying (CAG)115 to 157 repeat expansions develop pronounced neuronal intranuclear inclusions, containing the proteins huntingtin and ubiquitin, prior to developing a neurological phenotype.