The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies.
Kurt R. Brunden,Yuemang Yao,Justin S. Potuzak,Nuria Ibarz Ferrer,Carlo Ballatore,Michael J. James,Anne-Marie L. Hogan,John Q. Trojanowski,Amos B. Smith,Virginia M.-Y. Lee +9 more
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TLDR
Several MT-stabilizing compounds from the taxane and epothilone natural product families were examined to assess their membrane permeability and to determine whether they act as substrates or inhibitors of P-glycoprotein, and whether brain-penetrant compounds could stabilize mouse CNS MTs.About:
This article is published in Pharmacological Research.The article was published on 2011-04-01 and is currently open access. It has received 141 citations till now. The article focuses on the topics: Tauopathy & Membrane permeability.read more
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Journal ArticleDOI
The Microtubule-Stabilizing Agent, Epothilone D, Reduces Axonal Dysfunction, Neurotoxicity, Cognitive Deficits, and Alzheimer-Like Pathology in an Interventional Study with Aged Tau Transgenic Mice
Bin Zhang,Jenna C. Carroll,John Q. Trojanowski,Yuemang Yao,Michiyo Iba,Justin S. Potuzak,Anne-Marie L. Hogan,Sharon X. Xie,Carlo Ballatore,Amos B. Smith,Virginia M.-Y. Lee,Kurt R. Brunden +11 more
TL;DR: Data reveal that brain-penetrant MT-stabilizing drugs hold promise for the treatment of AD and related tauopathies, and that EpoD could be a candidate for clinical testing.
Book
Consciousness In The Universe
Stuart R. Hameroff,Roger Penrose +1 more
TL;DR: The proposed Orch OR suggests that there is a connection between the brain's biomolecular processes and the basic structure of the universe, and it is concluded that consciousness plays an intrinsic role in the universe.
Journal ArticleDOI
Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects.
Pascale Barbier,Orgeta Zejneli,Marlène Martinho,Alessia Lasorsa,Valérie Belle,Caroline Smet-Nocca,Philipp O. Tsvetkov,François Devred,Isabelle Landrieu +8 more
TL;DR: Since destabilization of MTs after dissociation of Tau could contribute to toxicity in neurodegenerative diseases, a molecular understanding of this interaction and its regulation is essential.
Journal ArticleDOI
Chronic stress exacerbates tau pathology, neurodegeneration, and cognitive performance through a corticotropin-releasing factor receptor-dependent mechanism in a transgenic mouse model of tauopathy.
Jenna C. Carroll,Michiyo Iba,Debbie A. Bangasser,Rita J. Valentino,Michael J. James,Kurt R. Brunden,Virginia M.-Y. Lee,John Q. Trojanowski +7 more
TL;DR: The results implicate HPA dysregulation in AD neuropathogenesis and suggest that prolonged stress may increase Aβ and tau hyperphosphorylation.
Journal ArticleDOI
Old Drugs as New Treatments for Neurodegenerative Diseases.
TL;DR: There is an urgent need for new treatments for this kind of disease, since the World Health Organization has predicted that neurodegenerative diseases affecting motor function will become the second-most prevalent cause of death in the next 20 years.
References
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Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Mike Hutton,Corinne Lendon,Patrizia Rizzu,Matt Baker,Susanne Froelich,Susanne Froelich,Henry Houlden,Stuart Pickering-Brown,Sumitra Chakraverty,Adrian M. Isaacs,Andrew Grover,J. Hackett,Jennifer Adamson,Sarah Lincoln,Dennis W. Dickson,Peter Davies,Ronald C. Petersen,M. Stevens,E. De Graaff,E. Wauters,J. Van Baren,M. Hillebrand,Marijke Joosse,J. M. Kwon,Petra Nowotny,Lien Kuei Che,Joanne Norton,John C. Morris,L. A. Reed,John Q. Trojanowski,Hans Basun,Lars Lannfelt,M. Neystat,Stanley Fahn,Frances Dark,Tony Tannenberg,Peter R. Dodd,Nicholas K. Hayward,John B.J. Kwok,Peter R. Schofield,Athena Andreadis,Julie S. Snowden,David Craufurd,David Neary,F. Owen,Ben A. Oostra,John Hardy,Alison Goate,J. C. van Swieten,David M. A. Mann,Timothy Lynch,Peter Heutink +51 more
TL;DR: In this paper, the authors sequenced tau in FTDP-17 families and identified three missense mutations (G272V, P301L and R406W) and three mutations in the 5' splice site of exon in
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Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
TL;DR: The severity of dementia was positively related to the number of NFTs in neocortex, but not to the degree of SP deposition, and N FTs accumulate in a consistent pattern reflecting hierarchic vulnerability of individual cytoarchitectural fields.
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Tau-mediated neurodegeneration in Alzheimer's disease and related disorders.
TL;DR: This Review summarizes the most recent advances in knowledge of the mechanisms of tau-mediated neurodegeneration to forge an integrated concept of those t Tau-linked disease processes that drive the onset and progression of AD and related tauopathies.
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Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yasumasa Yoshiyama,Makoto Higuchi,Bin Zhang,Shu-Ming Huang,Nobuhisa Iwata,Takaomi C. Saido,Jun Maeda,Tetsuya Suhara,John Q. Trojanowski,Virginia M.-Y. Lee +9 more
TL;DR: In this paper, the authors studied wild-type and P301S mutant human tau transgenic (Tg) mice and found that tangle formation was preceded by microglial activation.
Journal Article
Epothilones, a New Class of Microtubule-stabilizing Agents with a Taxol-like Mechanism of Action
Daniel M. Bollag,Patricia A. McQueney,Jian Zhu,Otto D. Hensens,Lawrence R. Koupal,Jerrold M. Liesch,Michael A. Goetz,Elias Lazarides,Catherine M. Woods +8 more
TL;DR: Epothilones represent a novel structural class of compounds, the first to be described since the original discovery ofTaxol, which not only mimic the biological effects of taxol but also appear to bind to the same microtubule-binding site as taxol.
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