Huntington's disease: underlying molecular mechanisms and emerging concepts.
TLDR
It is demonstrated that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins.About:
This article is published in Trends in Biochemical Sciences.The article was published on 2013-08-01 and is currently open access. It has received 302 citations till now. The article focuses on the topics: Huntingtin & Huntingtin Protein.read more
Citations
More filters
Journal ArticleDOI
The Biology of Proteostasis in Aging and Disease
TL;DR: The composition, function, and organizational properties of the PN are reviewed in the context of individual cells and entire organisms and the mechanisms by which disruption of thePN, and related stress response pathways, contributes to the initiation and progression of disease are discussed.
Journal ArticleDOI
Roles of tau protein in health and disease.
TL;DR: It is important to fully understand the range of neuronal functions attributed to tau, since this will provide vital information on its involvement in the development and pathogenesis of disease, and enable determination of which critical molecular pathways should be targeted by potential therapeutic agents developed for the treatment of tauopathies.
Journal ArticleDOI
Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications.
TL;DR: Novel antioxidants have shown great potential in mediating disease phenotypes and could be an area of interest for further research, as well as a highlight on the antioxidant-based therapies for alleviating disease severity.
Journal ArticleDOI
Integrated genomics and proteomics define huntingtin CAG length–dependent networks in mice
Peter Langfelder,Jeffrey P. Cantle,Jeffrey P. Cantle,Doxa Chatzopoulou,Nan Wang,Nan Wang,Fuying Gao,Fuying Gao,Ismael Al-Ramahi,Ismael Al-Ramahi,Xiao-Hong Lu,Xiao-Hong Lu,Eliana Marisa Ramos,Eliana Marisa Ramos,Karla El-Zein,Karla El-Zein,Yining Zhao,Sandeep Deverasetty,Andreas Tebbe,Christoph Schaab,Daniel J. Lavery,David Howland,Seung Kwak,Juan Botas,Juan Botas,Jeffrey S. Aaronson,Jim Rosinski,Giovanni Coppola,Steve Horvath,X. William Yang,X. William Yang +30 more
TL;DR: Proteomics was used to confirm 790 genes and 5 striatal modules with CAG length–dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo.
Journal ArticleDOI
In Situ Architecture and Cellular Interactions of PolyQ Inclusions
Felix J.B. Bäuerlein,Itika Saha,Archana Mishra,Maria Kalemanov,Antonio Martinez-Sanchez,Rüdiger Klein,Irina Dudanova,Mark S. Hipp,F. Ulrich Hartl,Wolfgang Baumeister,Rubén Fernández-Busnadiego +10 more
TL;DR: Advanced cryo-electron tomography methods suggest that aberrant interactions between fibrils and endomembranes contribute to the deleterious cellular effects of protein aggregation.
References
More filters
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
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.
Journal ArticleDOI
Adapting proteostasis for disease intervention.
TL;DR: The proteostasis network is described, a set of interacting activities that maintain the health of proteome and the organism that has the potential to ameliorate some of the most challenging diseases of this era.
Journal ArticleDOI
Unfolding the role of protein misfolding in neurodegenerative diseases.
TL;DR: The aim of this article is to review the literature on the molecular mechanism of protein misfolding and aggregation, its role in Neurodegeneration and the potential targets for therapeutic intervention in neurodegenerative diseases.
Journal ArticleDOI
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Joan S. Steffan,László Bodai,Judit Pallos,Marnix Poelman,Alexander McCampbell,Barbara L. Apostol,Alexsey Kazantsev,Emily Schmidt,Ya-Zhen Zhu,Marilee Greenwald,Riki Kurokawa,David E. Housman,George R. Jackson,J. Lawrence Marsh,Leslie M. Thompson +14 more
TL;DR: It is shown that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly binds the acetyltransferase domains of two distinct proteins: CREB-binding protein (CBP) and p300/CBP-associated factor (P/CAF).
Related Papers (5)
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
Marcy E. MacDonald,Christine Ambrose,Mabel P. Duyao,Richard H. Myers,Carol Lin,Lakshmi Srinidhi,Glenn Barnes,Sherryl A.M. Taylor,Marianne James,Nicolet Groot,Heather MacFarlane,Barbara Jenkins,Mary Anne Anderson,Nancy S. Wexler,James F. Gusella,Gillian P. Bates,Sarah Baxendale,Holger Hummerich,Susan F. Kirby,Mike North,S. Youngman,Richard Mott,Günther Zehetner,Zdenek Sedlacek,Annemarie Poustka,Anna-Maria Frischauf,Hans Lehrach,Alan Buckler,Deanna M. Church,Lynn Doucette-Stamm,Michael Conlon O'Donovan,Laura Riba-Ramirez,Manish A. Shah,Vincent P. Stanton,Scott A. Strobel,Karen M. Draths,Jennifer L. Wales,Peter B. Dervan,David E. Housman,Michael R. Altherr,Rita Shiang,Leslie M. Thompson,Thomas J. Fielder,John J. Wasmuth,Danilo A. Tagle,John Valdes,Lawrence W. Elmer,Marc W. Allard,Lucio H. Castilla,Manju Swaroop,Kris Blanchard,Francis S. Collins,Russell G. Snell,Tracey Holloway,Kathleen Gillespie,Nicole A. Datson,Duncan Shaw,Peter S. Harper +57 more
Huntington's disease: from molecular pathogenesis to clinical treatment
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