Genomes and Genes
Summary: Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.
Publications326 found, 100 shown here
- Propagation of tau pathology in a model of early Alzheimer's diseaseAlix de Calignon
MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Alzheimer s Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
Neuron 73:685-97. 2012..These data suggest that a sequence of progressive misfolding of tau proteins, circuit-based transfer to new cell populations, and deafferentation induced degeneration are part of a process of tau-induced neurodegeneration...
- Trans-synaptic spread of tau pathology in vivoLi Liu
Department of Pathology and Cell Biology, Taub Institute for Alzheimer s Disease Research, Columbia University, New York, New York, United States of America
PLoS ONE 7:e31302. 2012..In general, the mouse recapitulates the tauopathy that defines the early stages of AD and provides a model for testing mechanisms and functional outcomes associated with disease progression...
- Tau phosphorylation: the therapeutic challenge for neurodegenerative diseaseDiane P Hanger
MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
Trends Mol Med 15:112-9. 2009..tau is integral to the pathogenesis of Alzheimer's disease (AD), as well as several related disorders, termed tauopathies, in which tau is deposited in affected brain regions...
- Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathiesCeleste M Karch
Department of Psychiatry and Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Biol Chem 287:42751-62. 2012b>Tauopathies are a class of neurodegenerative diseases marked by intracellular aggregates of hyperphosphorylated Tau...
- MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathiesDaniah Trabzuni
Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK
Hum Mol Genet 21:4094-103. 2012....
- The role of tau (MAPT) in frontotemporal dementia and related tauopathiesR Rademakers
Department of Molecular Genetics, Neurogenetics Group, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
Hum Mutat 24:277-95. 2004..In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia...
- Tau fragmentation, aggregation and clearance: the dual role of lysosomal processingYipeng Wang
Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany
Hum Mol Genet 18:4153-70. 2009....
- Brain homogenates from human tauopathies induce tau inclusions in mouse brainFlorence Clavaguera
Department of Neuropathology, Institute of Pathology, University Hospital, 4031 Basel, Switzerland
Proc Natl Acad Sci U S A 110:9535-40. 2013..Here we injected brain extracts from humans who had died with various tauopathies into the hippocampus and cerebral cortex of ALZ17 mice...
- Regulation of tau pathology by the microglial fractalkine receptorKiran Bhaskar
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
Neuron 68:19-31. 2010..the hyperphosphorylated microtubule-associated protein tau (MAPT) are an invariant neuropathological feature of tauopathies. Here, we show that microglial neuroinflammation promotes MAPT phosphorylation and aggregation...
- Mutations causing neurodegenerative tauopathiesMichel Goedert
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
Biochim Biophys Acta 1739:240-50. 2005..of experimental animal models that reproduce the essential molecular and cellular features of the human tauopathies, including the formation of abundant filaments made of hyperphosphorylated tau protein and nerve cell ..
- The beta-propensity of Tau determines aggregation and synaptic loss in inducible mouse models of tauopathyKatrin Eckermann
Max Planck Unit for Structural Molecular Biology, Notkestrasse 85, 22607 Hamburg, Germany
J Biol Chem 282:31755-65. 2007Neurofibrillary lesions are characteristic for a group of human diseases, named tauopathies, which are characterized by prominent intracellular accumulations of abnormal filaments formed by the microtubule-associated protein Tau...
- Analysis of tau phosphorylation and truncation in a mouse model of human tauopathyPatrice Delobel
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK
Am J Pathol 172:123-31. 2008..and may be necessary for the assembly of tau into filaments in Alzheimer's disease and other tauopathies. Here we have investigated the time course of the appearance of phosphorylated and truncated tau in the brain ..
- Tau pathology in Alzheimer disease and other tauopathiesKhalid Iqbal
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
Biochim Biophys Acta 1739:198-210. 2005..It is this pathology which is characteristic of Alzheimer disease (AD) and other tauopathies. To date, the most established and the most compelling cause of dysfunctional tau in AD and other tauopathies ..
- Distinct tau prion strains propagate in cells and mice and define different tauopathiesDavid W Sanders
Department of Neurology, Washington University in St Louis, St Louis, MO 63105, USA
Neuron 82:1271-88. 2014Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations ("strains") in vivo that link structure to patterns of pathology...
- "Prion-like" templated misfolding in tauopathiesFlorence Clavaguera
Department of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland
Brain Pathol 23:342-9. 2013..insoluble and filamentous inclusions in a number of neurodegenerative diseases referred to as "tauopathies." In Alzheimer's disease, tau pathology develops in a stereotypical manner, with the first lesions appearing in ..
- Contrasting pathology of the stress granule proteins TIA-1 and G3BP in tauopathiesTara Vanderweyde
Department of Pharmacology, Boston University School of Medicine, Boston, Massachusetts 02118 2526, USA
J Neurosci 32:8270-83. 2012....
- Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's diseaseManuela Neumann
Institute of Neuropathology, Ludwig Maximilians University of Munich, Munich, Germany
Acta Neuropathol 107:489-96. 2004..antibodies against DJ-1, we have performed a comprehensive investigation of DJ-1 in alpha-synucleinopathies and tauopathies. DJ-1 was abundantly expressed in reactive astrocytes of patients with neurodegenerative diseases...
- The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological featuresEleanna Kara
Reta Lila Weston Laboratories and Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK
Neurobiol Aging 33:2231.e7-2231.e14. 2012..tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p...
- Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathiesConnie Luk
Reta Lila Weston Institute, UCL Institute of Neurology, London, UK
J Neurochem 123:396-405. 2012Characteristic tau isoform composition of the insoluble fibrillar tau inclusions define tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal dementia with parkinsonism linked to ..
- Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: effects on axonal viabilityLaura Gasparini
Cambridge Centre for Brain Repair, The University of Cambridge, Robinson Way, Forvie Site, Cambridge CB2 0PY, UK
Neurobiol Aging 32:419-33. 2011Tau inclusions play a key role in the pathogenesis of tauopathies. Altered tau levels have been detected in retina and optic nerve of patients with glaucoma, suggesting the possibility of shared pathogenic mechanisms with tauopathies...
- Comparison of family histories in FTLD subtypes and related tauopathiesJ S Goldman
Memory and Aging Center, University of California, San Francisco, CA 94117, USA
Neurology 65:1817-9. 2005..FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks...
- Tau-mediated neurodegeneration in Alzheimer's disease and related disordersCarlo Ballatore
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania 19104 4283, USA
Nat Rev Neurosci 8:663-72. 2007..our understanding of the mechanisms of tau-mediated neurodegeneration in Alzheimer's disease (AD) and related tauopathies, which are characterized by prominent CNS accumulations of fibrillar tau inclusions, are rapidly moving this ..
- Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L)Martin Ramsden
Department of Neurology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
J Neurosci 25:10637-47. 2005..Collectively, these data describe a novel transgenic mouse that closely mimics human tauopathy and may represent an important model for the future study of tau-related neurodegenerative disease...
- Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathiesKunihiro Uryu
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Neuropathol Exp Neurol 67:555-64. 2008..These findings provide further insight into the burden and clinical significance of TDP-43 pathology in disorders other than FTLD-U and amyotrophic lateral sclerosis...
- Changed conformation of mutant Tau-P301L underlies the moribund tauopathy, absent in progressive, nonlethal axonopathy of Tau-4R/2N transgenic miceDick Terwel
Experimental Genetics Group, Department of Human Genetics, KU Leuven, B 3000 Leuven, Belgium
J Biol Chem 280:3963-73. 2005..phosphorylation regulates binding to microtubules and, when disturbed by aging or mutations, results in diverse tauopathies and in neurodegeneration...
- Induction of tau pathology by intracerebral infusion of amyloid-beta -containing brain extract and by amyloid-beta deposition in APP x Tau transgenic miceTristan Bolmont
Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, Otfried Müller Str 27, D 72076 Tubingen, Germany
Am J Pathol 171:2012-20. 2007....
- Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodiesR De Silva
Reta Lila Weston Institute of Neurological Studies, University College London, and Department of Molecular Neuroscience and Neuropathology, Institute of Neurology, UK
Neuropathol Appl Neurobiol 29:288-302. 2003..containing fibrillar aggregates of hyperphosphorylated tau protein are a characteristic feature in the tauopathies, which include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17),..
- The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcriptsAmanda J Myers
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892 3707, USA
Neurobiol Dis 25:561-70. 2007..We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.
- AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathiesValérie Vingtdeux
Litwin Zucker Research Center for the Study of Alzheimer s Disease, The Feinstein Institute for Medical Research, North Shore LIJ, 350 Community Drive, Manhasset, NY 11030, USA
Acta Neuropathol 121:337-49. 2011b>Tauopathies represent a class of neurodegenerative disorders characterized by abnormal tau phosphorylation and aggregation into neuronal paired helical filaments (PHFs) and neurofibrillary tangles...
- Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathiesYoshinari Miyata
Department of Pathology and the Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
Future Med Chem 3:1523-37. 2011..that accumulates in at least 15 different neurodegenerative disorders, which are collectively referred to as tauopathies. In these diseases, tau is often hyperphosphorylated and found in aggregates, including paired helical ..
- Accumulation of pathological tau species and memory loss in a conditional model of tauopathyZdenek Berger
Mayo Clinic Jacksonville, Jacksonville, Florida 32224, USA
J Neurosci 27:3650-62. 2007Neurofibrillary tangles (NFTs) are a pathological hallmark of Alzheimer's disease and other tauopathies, but recent studies in a conditional mouse model of tauopathy (rTg4510) have suggested that NFT formation can be dissociated from ..
- Statins reduce the neurofibrillary tangle burden in a mouse model of tauopathyMoran Boimel
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, Israel
J Neuropathol Exp Neurol 68:314-25. 2009..Statins may provide therapy against NFTs in tauopathies, particularly when NFTs are the major neuropathologic component.
- The unfolded protein response is associated with early tau pathology in the hippocampus of tauopathiesDiana A T Nijholt
Department of Genome Analysis, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
J Pathol 226:693-702. 2012..The aim of the present study is to investigate UPR activation in sporadic tauopathies like progressive supranuclear palsy (PSP) and Pick's disease (PiD), and familial cases with frontotemporal ..
- Raphé tauopathy alters serotonin metabolism and breathing activity in terminal Tau.P301L mice: possible implications for tauopathies and Alzheimer's diseaseClement Menuet
Maturation, Plasticity, Physiology and Pathology of Respiration MP3 Respiration, Unité Mixte de Recherche 6231, Centre National de la Recherche Scientifique, Universite de la Mediterranee, Universite Paul Cezanne, Faculté Saint Jérôme Service 362, 13397 Marseille Cedex 20, France
Respir Physiol Neurobiol 178:290-303. 2011b>Tauopathies, including Alzheimer's disease are the most frequent neurodegenerative disorders in elderly people...
- Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathyKurt R Brunden
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurosci 30:13861-6. 2010..Accordingly, a possible therapeutic strategy for AD and related "tauopathies" is treatment with a MT-stabilizing anti-cancer drug such as paclitaxel...
- Protection against tauopathy by the drug candidates NAP (davunetide) and D-SAL: biochemical, cellular and behavioral aspectsNatalia Shiryaev
The Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv 69978, Israel
Curr Pharm Des 17:2603-12. 2011..These studies associate neuroprotection in vivo and in vitro and provide a broad base for future drug development based on NAP and D-SAL against multiple neurodegenerative conditions...
- Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutationWen Lang Lin
Mayo Clinic, Jacksonville, Florida, USA
Am J Pathol 162:213-8. 2003..Given similarities of the lesions in the mice to human neuronal and glial inclusions, these transgenic mice appear to be a valuable model to study pathogenesis of the neurodegenerative tauopathies.
- An okadaic acid-induced model of tauopathy and cognitive deficiencyZhang Zhang
Deptment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Brain Res 1359:233-46. 2010....
- Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathiesHanae Nakashima
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, 700 8558, Okayama, Japan
Acta Neuropathol 110:547-56. 2005..Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation...
- Transgenic Drosophila models of Alzheimer's disease and tauopathiesKanae Iijima-Ando
Laboratory of Neurogenetics and Pathobiology, Department of Biochemistry and Molecular Biology, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, JHN410, Philadelphia, PA, 19107, USA
Brain Struct Funct 214:245-62. 2010..dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases, so called tauopathies. Although most cases are sporadic, genes associated with familial AD and FTDP-17 have been identified, which ..
- Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathiesKurt R Brunden
Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104 4283, USA
Nat Rev Drug Discov 8:783-93. 2009..of the microtubule-associated protein tau are found in numerous neurodegenerative diseases, commonly known as tauopathies. In Alzheimer's disease - the most prevalent tauopathy - misfolded tau is probably a key pathological agent...
- Hyperdynamic microtubules, cognitive deficits, and pathology are improved in tau transgenic mice with low doses of the microtubule-stabilizing agent BMS-241027Donna M Barten
Neuroscience Drug Discovery, Bristol Myers Squibb, Wallingford, Connecticut 06492, USA
J Neurosci 32:7137-45. 2012Tau is a microtubule (MT)-stabilizing protein that is altered in Alzheimer's disease (AD) and other tauopathies. It is hypothesized that the hyperphosphorylated, conformationally altered, and multimeric forms of tau lead to a disruption ..
- mTOR regulates tau phosphorylation and degradation: implications for Alzheimer's disease and other tauopathiesAntonella Caccamo
Department of Physiology and The Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
Aging Cell 12:370-80. 2013Accumulation of tau is a critical event in several neurodegenerative disorders, collectively known as tauopathies, which include Alzheimer's disease and frontotemporal dementia...
- Tau promotes neurodegeneration via DRP1 mislocalization in vivoBRIAN DUBOFF
Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Neuron 75:618-32. 2012..Our results thus identify actin-mediated disruption of mitochondrial dynamics as a direct mechanism of tau toxicity in neurons in vivo...
- Cell-mediated neuroprotection in a mouse model of human tauopathyDavid W Hampton
Euan MacDonald Centre for Motor Neurone Disease Research, Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom
J Neurosci 30:9973-83. 2010..Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau...
- Passive immunization targeting pathological phospho-tau protein in a mouse model reduces functional decline and clears tau aggregates from the brainAllal Boutajangout
Department of Physiology and Neuroscience, New York University School of Medicine, New York, NY 10016, USA
J Neurochem 118:658-67. 2011Targeting hyperphosphorylated tau by immunotherapy is emerging as a promising approach to treat tauopathies such as Alzheimer's disease and frontotemporal dementia...
- Soluble tau species, not neurofibrillary aggregates, disrupt neural system integration in a tau transgenic modelLeora M Fox
Massachusetts General Hospital Harvard Medical School, MassGeneral Institute for Neurodegenerative Disease, Charlestown, 02129, USA
J Neuropathol Exp Neurol 70:588-95. 2011Neurofibrillary tangles are a feature of Alzheimer disease and other tauopathies, and although they are generally believed to be markers of neuronal pathology, there is little evidence evaluating whether tangles directly impact neuronal ..
- Tau pathology and future therapeuticsI Gozes
Laboratory for Molecular Neuroendocrinology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel
Curr Alzheimer Res 7:685-96. 2010....
- Upper airway dysfunction of Tau-P301L mice correlates with tauopathy in midbrain and ponto-medullary brainstem nucleiMathias Dutschmann
Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
J Neurosci 30:1810-21. 2010..Some primary tauopathies are linked to mutations in the MAPT gene coding for protein tau, but most are sporadic with unknown causes...
- Trehalose ameliorates dopaminergic and tau pathology in parkin deleted/tau overexpressing mice through autophagy activationJose A Rodriguez-Navarro
Department of Neurobiology, Hospital Ramon y Cajal, and CIBERned Madrid, Spain
Neurobiol Dis 39:423-38. 2010b>Tauopathies are neurodegenerative diseases, sporadic or familial, mainly characterized by dementia and parkinsonism associated to atrophy of the frontotemporal cortex and the basal ganglia, with deposition of abnormal tau in brain...
- Autophagic-lysosomal perturbation enhances tau aggregation in transfectants with induced wild-type tau expressionTadanori Hamano
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL, USA
Eur J Neurosci 27:1119-30. 2008..pathological hallmark shared by Alzheimer's disease and other neurodegenerative disorders known collectively as tauopathies. To model how tau fibrillogenesis evolves in tauopathies, we previously established transfectant M1C cultures ..
- Tau in Alzheimer disease and related tauopathiesK Iqbal
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
Curr Alzheimer Res 7:656-64. 2010..Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies.
- Kinesin-1 transport reductions enhance human tau hyperphosphorylation, aggregation and neurodegeneration in animal models of tauopathiesTomas L Falzone
Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Hum Mol Genet 19:4399-408. 2010..hyperphosphorylation and aggregation of the microtubule-associated protein tau defines neurodegenerative tauopathies. Destabilization of microtubules by loss of tau function and filament formation by toxic gain of function are ..
- Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathyKarin Boekhoorn
Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, 1098 SM Amsterdam, The Netherlands
J Neurosci 26:3514-23. 2006The microtubule binding protein tau is implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) with Parkinsonism caused by diverse mutations in the tau gene...
- Alzheimer's disease: old problem, new views from transgenic and viral modelsTomasz Jaworski
Experimental Genetics Group, LEGTEGG, Dept Human Genetics, KULeuven Campus Gasthuisberg ON1 06 602, Herestraat 49, B 3000 Leuven, Belgium
Biochim Biophys Acta 1802:808-18. 2010..We focus on specific aspects of single and multiple transgenic mouse models for Alzheimer's disease and for tauopathies, rather than providing an exhaustive list of all available models...
- Interneuronal transfer of human tau between Lamprey central neurons in situWonhee Kim
Department of Biological Sciences, Center for Cellular Neuroscience and Neurodegeneration Research, University of Massachusetts Lowell, Lowell, MA, USA
J Alzheimers Dis 19:647-64. 2010..interconnected parts of the brain are a potentially important but poorly understood component of human tauopathies such as Alzheimer's disease, Pick's disease, and corticobasal degeneration...
- Tau alternative splicing in familial and sporadic tauopathiesMichael Niblock
Department of Clinical Neuroscience, Institute of Psychiatry, King s College London, London, UK
Biochem Soc Trans 40:677-80. 2012..Tau alternative splicing could represent a target for therapeutic intervention to delay the progression of pathology in familial as well as sporadic tauopathies.
- Microglial activation in brain lesions with tau deposits: comparison of human tauopathies and tau transgenic mice TgTauP301LAtsushi Sasaki
Department of Human Pathology, Gunma University Graduate School of Medicine, Gunma, Japan
Brain Res 1214:159-68. 2008..to phosphorylated tau accumulation and the characteristics of microglial activation in brain lesions of human tauopathies in comparison to mutant tau transgenic (TG) mice...
- The microtubule-stabilizing agent, epothilone D, reduces axonal dysfunction, neurotoxicity, cognitive deficits, and Alzheimer-like pathology in an interventional study with aged tau transgenic miceBin Zhang
Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Neurosci 32:3601-11. 2012Neurodegenerative tauopathies, such as Alzheimer's disease (AD), are characterized by insoluble deposits of hyperphosphorylated tau protein within brain neurons...
- Pin1 colocalization with phosphorylated tau in Alzheimer's disease and other tauopathiesPankajavalli Ramakrishnan
F 526, Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Neurobiol Dis 14:251-64. 2003..Pin1 granules were sparse in PSP, and rarely did A-20 colocalize with TG-3. The appearance of Pin1 granules in the early stages of AD, PiD, and FTDP-17 (P301L) implicates Pin1 in their pathogenesis but not in PSP...
- Tau and tauopathiesGloria Lee
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA
Prog Mol Biol Transl Sci 107:263-93. 2012b>Tauopathies are age-related neurodegenerative diseases that are characterized by the presence of aggregates of abnormally phosphorylated tau...
- A new link to mitochondrial impairment in tauopathiesKathrin L Schulz
Department of Pharmacology, ZAFES, Biocenter, University of Frankfurt, 60438 Frankfurt, Germany
Mol Neurobiol 46:205-16. 2012b>Tauopathies like the "frontotemporal dementia with Parkinsonism linked to chromosome 17" (FTDP-17) are characterized by an aberrant accumulation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau...
- Globular glial tauopathies (GGT) presenting with motor neuron disease or frontotemporal dementia: an emerging group of 4-repeat tauopathiesZeshan Ahmed
Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, UCL Institute of Neurology, 1 Wakefield Street, London, WC1N 1PJ, UK
Acta Neuropathol 122:415-28. 2011..of tau in astrocytes are characteristic features that allow them to be distinguished from PSP and other tauopathies. We, therefore, propose the term globular glial tauopathy as an encompassing term to classify this emerging ..
- A neuroprotective role for the DNA damage checkpoint in tauopathyVikram Khurana
Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
Aging Cell 11:360-2. 2012..Surprisingly, checkpoint attenuation potently increases neurodegeneration through aberrant cell cycle re-entry of postmitotic neurons. These data suggest an unexpected neuroprotective role for the DNA damage checkpoint in tauopathies.
- Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's diseaseMasashi Kitazawa
Department of Neurobiology and Behavior, University of California Irvine, California 92697 4545, USA
J Neurosci 25:8843-53. 2005..Therefore, this study clearly demonstrates that microglial activation exacerbates key neuropathological features such as tangle formation...
- Important neuronal toxicity of microtubule-bound Tau in vivo in DrosophilaYasmina Talmat-Amar
CNRS, UMR 5203, Institut de Genomique Fonctionnelle, 141 rue de la Cardonille, Montpellier, France
Hum Mol Genet 20:3738-45. 2011..Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease...
- Axonal degeneration induced by targeted expression of mutant human tau in oligodendrocytes of transgenic mice that model glial tauopathiesMakoto Higuchi
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104
J Neurosci 25:9434-43. 2005Abundant filamentous tau inclusions in oligodendrocytes (OLGs) are hallmarks of neurodegenerative tauopathies, including sporadic corticobasal degeneration and hereditary frontotemporal dementia with parkinsonism linked to chromosome 17 (..
- Serum and cerebrospinal fluid urate levels in synucleinopathies versus tauopathiesR Constantinescu
Department of Neurology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden
Acta Neurol Scand 127:e8-12. 2013..Higher serum and cerebrospinal fluid (CSF) urate levels are associated with slower rates of clinical decline in PD and in multiple system atrophy (MSA)...
- Mechanistic studies unravel the complexity inherent in tau aggregation leading to Alzheimer's disease and the tauopathiesGayathri Ramachandran
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India
Biochemistry 52:4107-26. 2013..of the protein tau into amyloid fibrils is known to be involved in the causation of the neurodegenerative tauopathies and the progression of cognitive decline in Alzheimer's disease...
- Rapid accumulation of endogenous tau oligomers in a rat model of traumatic brain injury: possible link between traumatic brain injury and sporadic tauopathiesBridget E Hawkins
Sealy Center for Vaccine Development University of Texas Medical Branch, Galveston, Texas 77555, USA
J Biol Chem 288:17042-50. 2013..These findings suggest that diagnostic tools and therapeutics that target only toxic forms of Tau may provide earlier detection and safe, more effective treatments for tauopathies associated with repetitive neurotrauma.
- A novel organotypic tauopathy model on a new microcavity chip for bioelectronic label-free and real time monitoringDana Krinke
Centre for Biotechnology and Biomedicine BBZ, University of Leipzig, Division of Molecular Biological Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany
Biosens Bioelectron 26:162-8. 2010..Moreover, we were able to detect and quantify distinct, AD-related effects triggered by tau-mutant (P301L) expression and hyperphosphorylation in our organotypic 3D-cultures with the help of impedance spectroscopy...
- Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathiesAdriana Ferreira
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Mol Med 17:676-85. 2011Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected ..
- Cascade of tau toxicity in inducible hippocampal brain slices and prevention by aggregation inhibitorsLars Messing
German Center for Neurodegenerative Diseases DZNE, Bonn, Germany
Neurobiol Aging 34:1343-54. 2013Mislocalization and aggregation of the axonal protein tau are hallmarks of Alzheimer's disease and other tauopathies. Here, we studied the relationship between tau aggregation, loss of spines and neurons, and reversibility by aggregation ..
- Unclassifiable tauopathy associated with an A152T variation in MAPT exon 7G G Kovacs
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Clin Neuropathol 30:3-10. 2011..Our observation of an apparently familial disorder with a novel neuropathological phenotype suggests a possible pathogenic role of this MAPT gene variation, which might be different from mutations affecting the microtubule binding...
- Is tau ready for admission to the prion club?Garth F Hall
Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA, USA
Prion 6:223-33. 2012....
- Drosophila models of human tauopathies indicate that Tau protein toxicity in vivo is mediated by soluble cytosolic phosphorylated forms of the proteinSébastien Feuillette
INSERM U614, Rouen Institute for Medical Research, Faculty of Medicine, University of Rouen, Rouen Cedex, France
J Neurochem 113:895-903. 2010Tau is a neuronal microtubule-associated protein involved in microtubules assembly and stabilization. Tauopathies, including Alzheimer's disease and fronto-temporal dementia with parkinsonism linked to chromosome 17, are a group of ..
- Modulation of protein-protein interactions as a therapeutic strategy for the treatment of neurodegenerative tauopathiesC Ballatore
Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th St, Philadelphia, PA 19104 6323, USA
Curr Top Med Chem 11:317-30. 2011..and unresolved issues surrounding the development of novel therapeutics for the treatment of neurodegenerative tauopathies, which are based on (A) MT-stabilizing agents to compensate for the loss of normal tau function, and (B) small ..
- Tau isoform composition influences rate and extent of filament formationQi Zhong
Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
J Biol Chem 287:20711-9. 2012..In general, aggregation propensity correlated with genetic risk reported for multiple tauopathies, implicating aggregation as one candidate mechanism rationalizing the correlation between Tau expression ..
- Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathyMichiyo Iba
Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Neurosci 33:1024-37. 2013b>Tauopathies, including Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau pathologies, are neurodegenerative diseases characterized by neurofibrillary tangles (NFTs) comprising filamentous tau protein...
- Filamin-A and Myosin VI colocalize with fibrillary Tau protein in Alzheimer's disease and FTDP-17 brainsSébastien Feuillette
INSERM U614, Institute for Biomedical Research, Faculty of Medicine, University of Rouen, Rouen, France
Brain Res 1345:182-9. 2010b>Tauopathies, including Alzheimer's disease (AD), fronto-temporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), Pick's disease and progressive supranuclear palsy, are neurodegenerative disorders neuropathologically ..
- Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic miceDick Terwel
Experimental Genetics Group, Department Human Genetics, Katholieke Universiteit Leuven Campus Gasthuisberg ON1 06 602, B 3000 Leuven, Belgium
Am J Pathol 172:786-98. 2008..The data indicate that amyloid induces tauopathy through activation of GSK-3 and suggest a role for the kinase in maintaining the functional integrity of adult neurons...
- Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse signals require the tumor suppressor protein LKB1Ji Wu Wang
Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education, and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
J Neurosci 27:574-81. 2007..These results reveal a new function for the tumor suppressor protein LKB1 in a signaling cascade through which the phosphorylation and function of tau is regulated by diverse signals under physiological and pathological conditions...
- TauopathiesF Hernandez
Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Fac Ciencias, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
Cell Mol Life Sci 64:2219-33. 2007..of its isoforms could provoke pathological effects resulting in the appearance of neuronal disorders known as tauopathies. The purpose of this work is to review the possible mechanisms for tau alterations that could lead to the onset ..
- Tau and tauopathiesM Robert
Department of Neurology, Medical College, Trivandrum, Kerala, India
Neurol India 55:11-6. 2007..neuronal, oligodendroglial or astrocytic filamentous tau inclusions are now grouped under the common rubric of tauopathies. The discovery of mutations in the tau gene, located on Chromosome 17 and its relationship to frontotemporal ..
- Tauopathies with parkinsonism: clinical spectrum, neuropathologic basis, biological markers, and treatment optionsA C Ludolph
Department of Neurology, University of Ulm, Ulm, Germany
Eur J Neurol 16:297-309. 2009b>Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system...
- Posttranslational modifications of tau--role in human tauopathies and modeling in transgenic animalsFeng Chen
Division of Psychiatry Research, University of Zurich, August Forel Str 1, 8008 Zurich, Switzerland
Curr Drug Targets 5:503-15. 2004..of scant or no beta-amyloid plaques characterizes additional neurodegenerative disorders collectively called tauopathies. In the course of plaque and NFT formation, the major proteinaceous components of these lesions undergo post-..
- Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathyVeronique Schaeffer
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
Brain 135:2169-77. 2012The accumulation of insoluble proteins is a pathological hallmark of several neurodegenerative disorders. Tauopathies are caused by the dysfunction and aggregation of tau protein and an impairment of cellular protein degradation pathways ..
- Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathiesDavid J Irwin
Centre for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Alzheimer s Disease Core Centre, Institute on Ageing, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6021, USA
Brain 135:807-18. 2012..component of neurofibrillary inclusions characteristic of Alzheimer's disease and related neurodegenerative tauopathies. When tau fibrillizes, it undergoes abnormal post-translational modifications resulting in decreased solubility ..
- Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tanglesJing L Guo
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 286:15317-31. 2011Neurofibrillary tangles (NFTs) in Alzheimer disease and related tauopathies are composed of insoluble hyperphosphorylated Tau protein, but the mechanisms underlying the conversion of highly soluble Tau into insoluble NFTs remain elusive...
- Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tauWen Lang Lin
Mayo Clinic, Jacksonville, Florida 32224, USA
J Neurocytol 32:1091-105. 2003..The other type resembled ballooned neurons seen in some human tauopathies. The nucleus was peripherally placed, but normal appearing...
- Familial FTDP-17 missense mutations inhibit microtubule assembly-promoting activity of tau by increasing phosphorylation at Ser202 in vitroDong Han
Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital
J Biol Chem 284:13422-33. 2009In Alzheimer disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and other tauopathies, tau accumulates and forms paired helical filaments (PHFs) in the brain...
- The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathyGünter U Höglinger
INSERM U679, Hopital de la Salpetriere, Paris, France
J Neurochem 95:930-9. 2005..Our data suggest that chronic respiratory chain dysfunction might trigger a form of neurodegeneration in which accumulation of hyperphosphorylated tau protein predominates over deposits of alpha-synuclein...
- CHIP-Hsc70 complex ubiquitinates phosphorylated tau and enhances cell survivalHideki Shimura
Department of Neurology, Harvard Medical School and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
J Biol Chem 279:4869-76. 2004..CHIP could rescue phosphorylated tau-induced cell death, and therefore the CHIP-Hsc70 complex may provide a new therapeutic target for the tauopathies.
- Progressive neurodegeneration in C. elegans model of tauopathyTomohiro Miyasaka
Department of Neuropathology, Faculty of Medicine, University of Tokyo, 7 3 1 Hongo, Tokyo 113 0033, Japan
Neurobiol Dis 20:372-83. 2005..Expression of GSK3 brought about slight deterioration in the touch response, while expression of HSP70 led to some improvement...
- Inducible expression of Tau repeat domain in cell models of tauopathy: aggregation is toxic to cells but can be reversed by inhibitor drugsInna Khlistunova
Max Planck Unit for Structural Molecular Biology, DESY, Hamburg, Germany
J Biol Chem 281:1205-14. 2006....
- Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathyTara L Spires
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown 02129, USA
Am J Pathol 168:1598-607. 2006..Together, these results imply that neurofibrillary tangles do not necessarily lead to neuronal death...
- An R5L tau mutation in a subject with a progressive supranuclear palsy phenotypeParvoneh Poorkaj
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, Seattle, WA 98195, USA
Ann Neurol 52:511-6. 2002..Insoluble tau from cortical regions also contained 1N3R tau. Thus, the R5L mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism...
- Assembly of tau in transgenic animals expressing P301L tau: alteration of phosphorylation and solubilityNaruhiko Sahara
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
J Neurochem 83:1498-508. 2002..The results suggest that tau in S2 represents an intermediate from which insoluble tau is derived, and that phosphorylation may play a role in filament formation and/or stabilization...
- Identification of common variants influencing risk of the tauopathy progressive supranuclear palsyGünter U Höglinger
Department of Neurology, Philipps Universitat, Marburg, Germany
Nat Genet 43:699-705. 2011..Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease...
- Neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathyBrian C Kraemer
Geriatrics Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA 98108 1597, USA
Proc Natl Acad Sci U S A 100:9980-5. 2003..soluble and insoluble tau is phosphorylated at many of the sites hyperphosphorylated in FTDP-17, AD, and other tauopathies. Substantial neurodegeneration, seen as bulges and gaps in nerve cords followed by loss of neurons, occurs ..
- Transgenic mouse model of tauopathies with glial pathology and nervous system degenerationMakoto Higuchi
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Neuron 35:433-46. 2002..including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), are neurodegenerative tauopathies characterized by widespread CNS neuronal and glial tau pathologies, but there are no tau transgenic (Tg) mice ..
- Mechanism of CD40 signaling to APP metabolismMichael J Mullan; Fiscal Year: 2013..We have identified CD40 signaling as a potentially key modulator of both amyloid and tau pathology and this proposal seeks to identify downstream molecules which are more tractable from a drug development perspective. ..
- A Diarylheptanoid Scaffold to Treat TaopathiesChad A Dickey; Fiscal Year: 2013..screen as a potent reducer of the structural protein tau, which accumulates in a group of diseases called the "tauopathies"...
- Immunotherapy against tauopathy in a transgenic mouse modelDavid Morgan; Fiscal Year: 2013..These experiments will use antibodies that bind to the tau protein in an attempt to eliminate it from the brain. This may lead to use of similar antibodies or possible vaccines to treat patients with these diseases. ..
- A kinase pathway required for cortical neuron polarizationFranck Polleux; Fiscal Year: 2012..Recent evidence suggested that LKB1 disruption could participate to tauopathies such as Alzheimer's disease...
- TDP-43 acetylation as a pathogenic modification in ALS &related proteinopathiesTODD JONATHAN COHEN; Fiscal Year: 2013..that acetylation of the tau protein promotes tangle formation in Alzheimer's disease and related tauopathies (Nat Commun. 2011~2:252)...
- Mechanisms Underlying Tauopathy Following Traumatic Brain InjuryDavid Brody; Fiscal Year: 2013..The worldwide interest in athletes and military personnel with tau pathology and chronic traumatic encephalopathy underscores the urgency of this line of investigation. ..
- Identifying and characterizing gene(s) involved in beta-amyloid production.Huaxi Xu; Fiscal Year: 2013..a major cause of AD, whereas hyperphosphorylated tau has been found in many neurodegenerative diseases known as tauopathies. Hence, identification of new genes/proteins involved in these processes is a major goal in AD research and may ..
- CLINICAL CORRELATES OF LONGITUDINAL PET CHANGES IN ADMony J de Leon; Fiscal Year: 2013..This project will test the hypothesis that validated biological markers for neurofibrillary tangle and amyloid plaque pathology contribute to FDG-PET in predicting future cognitive decline in cognitively normal subjects. ..
- Autophagic Clearance of Aberrant Tau: Biochemical and Therapeutic ImplicationsKaren E Duff; Fiscal Year: 2013..1 will examine the interplay between the UPS, AL-S and tau accumulation in human tissue from patients with 4R tauopathies and will compare to two mouse models of 4R tauopathy that have been modified to express an autophagic marker...
- Polyphenolic Interventions for tau Pathogenesis in Alzheimers ModelsSALLY ANN FRAUTSCHY; Fiscal Year: 2013..Completion of aims will move the field forward in demonstrating interrelationship between tau aggregation, synapto/neuro-protection, inflammation, autophagy and the HSPs. ..
- Polarized transport in nervous system development and disease in zebrafishPhilip Campbell; Fiscal Year: 2013..NDs) represent a group of diseases including Alzheimer's disease, Parkinson's disease, and various tauopathies, characterized by similar phenotypic manifestations...
- MSUT2/SUT2 controls tau protein aggregation and neurotoxicity.Brian C Kraemer; Fiscal Year: 2013..To better understand how abnormal tau contributes to neurodegeneration in AD and other tauopathies, we have established a model in C. elegans for tau aggregation and consequent neurodegeneration...
- Identification of Novel Small Molecules as Tau Protein Aggregation Inhibitors forALAN D SNOW; Fiscal Year: 2011..of tau aggregation/fibrillogenesis, and may have great potential as new therapeutic agents for AD and other tauopathies.] The major objective our proposal is to identify specific small molecule compounds from ProteoTech's ..
- Autoimmune biomarker profiling in tauopathyIrving E Vega; Fiscal Year: 2013DESCRIPTION (provided by applicant): Tauopathies are a family of neurodegenerative disorders characterized by the intracellular aggregation of filaments predominantly composed of hyperphosphorylated microtubule-associated protein tau...
- Tyrosine Phosphorylation in Alzheimer's DiseaseGloria Lee; Fiscal Year: 2013..Moreover, AD is now considered a "tauopathy". To discover new biomarkers and therapeutics for AD and other tauopathies, it is critical to determine how tau causes disease...
- Tau Nitration and Oxidation in Alzheimer's DiseaseLESTER IRVIN BINDER; Fiscal Year: 2010..nitrated sites on tau to assess the timing and role of nitrative events during the course of AD and other tauopathies. We will also produce monoclonal antibodies to additional nitrated sites on tau and assess them in diseased ..
- Peripheral TGF-beta Pathway Inhibitor Therapy in Alzheimer's RatsTerrence Town; Fiscal Year: 2013....
- Characterization of Small Molecule Splicing Modulators of MAPT and FGFR1Erik S Anderson; Fiscal Year: 2011..b>Tauopathies, which are a set of neurodegenerative diseases characterized by altered splicing of microtubule associated ..
- A novel therapeutic approach to lowering tau and its impact on tauopathiesNASSER HUSSEIN ZAWIA; Fiscal Year: 2013..Neurofibrillary degeneration in the absence of [unreadable]- amyloid, is also seen in several tauopathies such as Guam parkinsonism dementia complex, dementia pugilistica, corticobasal degeneration, Pick's ..
- Pathogenic events triggered by tau acetylation in neurodegenerative tauopathyTara Tracy; Fiscal Year: 2013DESCRIPTION (provided by applicant): Tauopathies are a class of age-related neurodegenerative diseases that millions of people in our country suffer from today...
- Canonical Wnt Signaling by the Proteolytc Processing of LRP6BRANDON RICHARD BEAGLE; Fiscal Year: 2010..and has been implicated in generating aberrantly hyperphosporylated tau proteins associated with AD and other tauopathies. Hence, identifying the mechanisms and proteins that regulate GSK3 activity will provide pertinent pathological ..
- ROLE OF HSP 110 IN TAUOPATHYNahid F Mivechi; Fiscal Year: 2013..The neuropathological hallmarks of AD and other tauopathies include accumulation of senile plaques and/or neurofibrillary tangles (NFTs) that causes neurons to degenerate...
- Mouse Models with Regulatable Cell Type-specific Expression of Anti-Tau shRNAsLennart Mucke; Fiscal Year: 2012..in Alzheimer's disease (AD) and a variety of other neurological conditions collectively referred to as tauopathies. Remarkably, the functions tau fulfills in the adult brain and the exact roles it plays in the pathogenesis of ..
- The unfolded protein response and neurodegenerative tauopathiesLauren D Stutzbach; Fiscal Year: 2013..Aim 3 will make use of human lymphoblastoid cell lines to determine how protein coding changes in the PERK protein affect its function as part of the UPR. ..
- Tau Protein Aggregation Inhibitors for TauopathiesALAN D SNOW; Fiscal Year: 2013..aromatic compounds can also serve as direct inhibitors of tau aggregation/fibrillogenesis in mouse models of tauopathies. These compounds are believed to possess great potential as new therapeutic agents for AD and related ..
- Frontal Lobe Neuroimaging as a Biomarker of Chronic Traumatic EncephalopathyJULIE MARIE STAMM; Fiscal Year: 2012..This study is part of a larger study, which is the first to address these issues and, therefore, may have a considerable impact on public health. ..
- The role of fractalkine signaling in neurodegenerative diseaseRichard M Ransohoff; Fiscal Year: 2013..Similarly in non-AD tauopathies, there is both abundant MAPT pathology and neuroinflammation...
- Development of Zebrafish Taupoathy Models for Translational ResearchEDWARD ALAN BURTON; Fiscal Year: 2013..be a valuable tool for translational studies to develop new therapies for PSP and CBD, and potentially other Tauopathies such as Alzheimer's disease and chronic head injury...
- Chemical Probes and Chaperone-Accelerated Turnover of TauJason E Gestwicki; Fiscal Year: 2013..Thus, strategies for accelerating the removal of abnormal tau are expected to protect against tauopathies. Cellular protein quality control (PQC) pathways, including molecular chaperones, have been shown to regulate ..
- The role of a novel tau-associated protein in neurodegenerationIrving E Vega; Fiscal Year: 2012b>Tauopathies are a family of neurodegenerative disorders characterized by the intracellular aggregation of filaments derived from hyperphosphorylated microtubule-associated protein tau...
- Alzhelmer's Disease Drug Development ProgramAmos B Smith; Fiscal Year: 2012..system (CMS) are sequestered into filamentous inclusions that are the signature lesions of AD and related tauopathies, thereby compromising the normal function of tau in stabilizing and maintaining MT networks essential for ..
- The role of microglial-and neuron-specific MyD88 signaling in tauopathiesKiran Bhaskar; Fiscal Year: 2013..of microtubule-associated protein tau (MAPT) and neurodegeneration are hallmarks of many neurodegenerative tauopathies. Although, the exact etiology of many of these tauopathies remains elusive, neuropathologically, they are ..
- Chronic Traumatic Encephalopathy: Clinical Presentation and BiomarkersRobert A Stern; Fiscal Year: 2013..abstract_text> ..
- Epitope-Specific Targeting of Tau Aggregates.Einar M Sigurdsson; Fiscal Year: 2013..tau protein has recently become attractive as a potential therapy for Alzheimer's disease (AD) and related tauopathies. We previously showed that active immunization targeting a disease-related phospho-tau epitope reduces cerebral ..
- Genetic and Environmental Risk Factors for PSPIrene Litvan; Fiscal Year: 2010..Understanding the etiology of PSP may also help explain the causes of other tauopathies such as Alzheimer's disease...
- Parkin protection in gene transfer animal models (KO-1 Award)Charbel Moussa; Fiscal Year: 2012..an important pathological landmark in Parkinson's disease [PD], Alzheimer's disease [AD] and the tauopathies with Parkinsonism...
- PTEN, Cell Cycle and Neurofibrillary DegenerationFrancesca Fang Liao; Fiscal Year: 2012..Although NFTs are coincident with cell death in several neurodegenerative diseases, known as tauopathies, and most notably in AD, the molecular mechanisms leading to this chronic loss of neuronal cells is still not ..
- The Hsp90 cochaperone FKBP51 regulates tau structure and functionChad A Dickey; Fiscal Year: 2013..tau and whether it is a rational therapeutic target for treating AD, Parkinson's disease (PD), and other tauopathies. Tau aggregation is a central component of Alzheimer's disease (AD) and ~15 other neurodegenerative ..
- Endosomal-Lysosomal Function in Neuronal Storage DiseaseSTEVEN UPSHAW WALKLEY; Fiscal Year: 2013....
- The Role of Monocytes and Microglia in Traumatic Brain Injury-Induced TauopathiesRichard M Ransohoff; Fiscal Year: 2013..exposed to TBI are at a greatly increased risk for developing a number of neurodegenerative diseases termed tauopathies, including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE)...
- Clearance and In Vivo Detection of Tau PathologyEinar M Sigurdsson; Fiscal Year: 2013..Obviously, tau pathology is another important target in AD, and the primary one in other tauopathies. Presence of pathological tau correlates much better with the degree of dementia than A[unreadable] deposition...
- Gene discovery in PSP by transcriptome, neuropathology and sequence analysisNilufer Ertekin-Taner; Fiscal Year: 2013..Given the clinicopathological overlap between PSP and other tauopathies, our proposal is expected to impact a wide range of neurodegenerative disorders and generate novel therapeutic ..
- Pharmacological modulation of tau neurotoxicity in vivoMel B Feany; Fiscal Year: 2012..We now propose using our model of Alzheimer's disease and related tauopathies to identify drugs that can ameliorate neurotoxicity in vivo...
- INVESTIGATIONS OF DEMENTIA IN PARKINSON DISEASEJOEL SYNES PERLMUTTER; Fiscal Year: 2013..These steps are critical for development of effective treatment of dementia associated with PD. ..
- GENETICS AND MOLECULAR BIOLOGY OF PARKINSONISMDENNIS WILLIAM DICKSON; Fiscal Year: 2013..tau is related PD and how tau-directed therapies may translate into novel treatments for PD and parkinsonian tauopathies. The proposed Center will have three projects and four cores with an overarching theme to understand the role ..
- Hyperphosphorylated tau as drug targetMin Hao Kuo; Fiscal Year: 2012..AD and several other devastating neurodegenerative disorders are collectively known as tauopathies in which the tau protein becomes pathologically hyperphosphorylated and aggregates into the neurofibrillary ..
- Role of Tau Cleavage in TauopathyKaren H Ashe; Fiscal Year: 2013This project aims to validate a novel drug target for tauopathies [unreadable] a group of incurable neurodegenerative conditions that includes Alzheimer[unreadable]s disease (AD)...
- Tau-mediated chromatin regulation and neurodegenerationSUSAN E FROST; Fiscal Year: 2012..the most frequent form of dementia, and over twenty other neurodegenerative diseases, collectively termed "tauopathies." There is currently no disease-modifying treatment available for AD or other tauopathies...
- High-Throughput Nanoscale Approaches to Studying and Inhibiting Amyloid ToxicityTimothy Lu; Fiscal Year: 2011..this system can be applied to discover peptide inhibitors of other diseases, such as viral infections and tauopathies. This high-throughput platform is enabled by our expertise in synthetic biology and bacterial engineering...
- Developing neuroprotective strategies for proteinopathy: a comparative modelingBrian C Kraemer; Fiscal Year: 2013..The long term goal of this work is to develop neuroprotective strategies for neurodegenerative disorders with TPD-43 and tau protein deposits. ..
- Kinases Linking Abeta and Tau to Synaptic DysfunctionLennart Mucke; Fiscal Year: 2013..frontotemporal lobar degeneration (FTLD) and a variety of other neurodegenerative conditions referred to as "tauopathies." Preliminary data obtained during the preceding funding period suggest that neuronal and behavioral ..
- Tracking the Propagation of Misfolded Tau: A Study of Cellular Uptake and TrafficBRANDON BLAKE HOLMES; Fiscal Year: 2013DESCRIPTION (provided by applicant): Tauopathies are a class of neurodegenerative disorders characterized by the pathological accumulation of microtubule-associated protein tau in the human brain...
- Prolyl Isomerase Pin 1 and NeurodegenerationKun Ping Lu; Fiscal Year: 2009..assembly, little is known about what phosphorylation actually does and how it affects the pathogenesis of the tauopathies. Interestingly, pSer/Thr- Pro motifs in proteins exist in distinct cis and trans conformations, whose ..
- High throughput tau oligomer drug screening assay for Alzheimer's diseaseJames G Moe; Fiscal Year: 2013..least three or more lead candidate compounds targeting tau oligomers for evaluation in animal models of AD and tauopathies. To attain this result, secondary screening in cell models of tau oligomer formation and medicinal chemistry ..
- A Mouse Model of Tau Pathology in AD and Other DementiasPETER P DAVIES; Fiscal Year: 2013..efficacy raises many questions that will need to be addressed before this approach can be tested in humans with tauopathies, not the least of which is the nature of the antibody required for efficacy...
- Biological and Pathological Interactions between Tau and LRRK2JADA M LEWIS; Fiscal Year: 2013..be disrupted as it becomes hyperphosphorylated and aggregated in a family of neurodegenerative diseases termed tauopathies. Tau mutation is causative for the tauopathy frontotemporal dementia and parkinsonism linked to chromosome 17 (..
- Elucidating the Pathology of Impact-Induced Traumatic Brain InjuryCHAD ALAN TAGGE; Fiscal Year: 2013..Insight gained from this work will also facilitate development of urgently needed diagnostics and therapeutics for these devastating disorders. ..
- Molecular determinants of lamin a accumulation in human aging and diseaseAgnieszka Kalinowski; Fiscal Year: 2012..other pathologies that result from destructive protein-membrane interactions, such as Alzheimer's disease, tauopathies and prion diseases...
- Inhibition of Hsp70 ATPase activity reduces tau through the cellular degradationJOHN CLARENCE O'LEARY; Fiscal Year: 2013..the microtubule associated protein tau, abnormally aggregates in numerous neurodegenerative diseases termed tauopathies. Some chaperone proteins have shown auspicious results as therapeutic targets in models of tauopathy...
- CELL-CELL TRANSFER AND PROPAGATION OF TAU AGGREGATESMarc I Diamond; Fiscal Year: 2013DESCRIPTION (provided by applicant): Cell-cell transfer and propagation of tau aggregates. Tauopathies are devastating neurodegenerative diseases...
- Phosphoprotein phosphatase 2A, a new target for Alzheimer's Disease interventioSTEVEN BRAITHWAITE; Fiscal Year: 2010..Abnormal hyperphosphorylation of tau plays an important role in Alzheimer's disease (AD) and other tauopathies. Current therapeutic approaches with focus on tau kinases (e.g...
- Genetic Determinants of TauopathiesJason Chen; Fiscal Year: 2013..are still unclear, variants in the MAPT gene, encoding for tau, have been identified as causal in some tauopathies, and the H1 haplotype at the 17q21...
- Colloquium on the Cytoskeleton and Human DiseaseLeslie Wilson; Fiscal Year: 2001..new compounds), 2)microtubule-associated proteins and neurodegenerative disease (Alzheimer's disease and other tauopathies, new concepts and new targets), 3)intermediate filaments and disease (keratin and skin diseases, desmin in ..
- BIOLOGY OF CHROMOSOME 17 LINKED DEMENTIA WITH TAUOPATHYJill Murrell; Fiscal Year: 2000..The members of the team are highly experienced investigators in their field of endeavor. ..
- Tau phosphorylation and neurodegenerationAlejandra del C Alonso; Fiscal Year: 2009..in vitro results and of different tau phosphorylation sites will provide an explanation of the progression of tauopathies and it will identify new therapeutic targets for neurodegenerative diseases...
- Modeling Human Tauopathies in Drosophila melanogasterGena Heidary; Fiscal Year: 2003..melanogaster to determine the role of the microtubule-associated protein (MAP) tau in the pathogenesis of human tauopathies. The tau protein has been implicated in at least 20 neurodegenerative diseases collectively referred to as ..
- MECHANISM AND CONTROL OF BRAIN MICROTUBULE DYNAMICSLeslie Wilson; Fiscal Year: 2009..how the tau proteins, which stabilize microtubules and may mis-regulate dynamics in neurodegenerative tauopathies such as Frontotemporal Dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and the stathmin/SCG10 ..
- Role of PP2A in tauopathiesEstelle Sontag; Fiscal Year: 2006..the hypothesis that their disruption promotes the accumulation of hyperphosphorylated forms of tau in all tauopathies. The first aim will focus on establishing major properties of PP2A/tau and PP2A/MT interactions in vitro and in ..
- Role of PP2A in tauopathiesEstelle Sontag; Fiscal Year: 2007..PP2A in human brain regions during normal aging, and assess whether it becomes altered in AD and other tauopathies. If our model is validated, dietary folate supplementation and PPMT may be novel therapeutic targets for ..
- Biology of Tauopathies Studied with HSV AmpliconsE Antonio Chiocca; Fiscal Year: 2007..unreadable] [unreadable]..
- Genetic Analysis of Tau H1 in ParkinsonismMatthew Farrer; Fiscal Year: 2006DESCRIPTION (provided by applicant): The tau H1 association in 4R tauopathies, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), is fundamental to their etiology, yet the underlying mutation(s) and ..
- Development of Radiopharmaceuticals for Imaging Brain Tau PathologyDaniel Skovronsky; Fiscal Year: 2009..of Alzheimer's disease and for 2) Improving early and accurate diagnosis of Alzheimer's and related tauopathies. To test this hypothesis, we will screen for and develop a novel 18F-labeled radiopharmaceutical to ..