Kurt R Brunden

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biochem Soc Trans 40:661-6. 2012
  2. pmc Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy
    Kurt 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
  3. pmc Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Institute on Aging, and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Exp Neurol 223:304-10. 2010
  4. pmc Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies
    Kurt 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
  5. pmc The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies
    Kurt R Brunden
    Center for Neurodegenerative Disease Research and Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
    Pharmacol Res 63:341-51. 2011
  6. pmc 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
    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. 2012
  7. doi request reprint Aminothienopyridazine inhibitors of tau aggregation: evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties
    Carlo Ballatore
    Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, USA
    Bioorg Med Chem 20:4451-61. 2012
  8. pmc Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of tau aggregation
    Carlo Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    J Med Chem 53:3739-47. 2010
  9. pmc Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation
    Alex Crowe
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 288:11024-37. 2013
  10. pmc Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies
    Carlo Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, United States
    J Med Chem 55:8979-96. 2012

Collaborators

Detail Information

Publications23

  1. pmc Brain-penetrant microtubule-stabilizing compounds as potential therapeutic agents for tauopathies
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Biochem Soc Trans 40:661-6. 2012
    ..Importantly, no adverse side effects were observed in the EpoD-treated mice. These results suggest that EpoD might be a viable drug candidate for the treatment of AD and related tauopathies...
  2. pmc Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy
    Kurt 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
    ..These results suggest that certain brain-penetrant MT-stabilizing agents might provide a viable therapeutic strategy for the treatment of AD and FTDs...
  3. pmc Tau-directed drug discovery for Alzheimer's disease and related tauopathies: a focus on tau assembly inhibitors
    Kurt R Brunden
    Center for Neurodegenerative Disease Research, Institute on Aging, and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Exp Neurol 223:304-10. 2010
    ..We briefly review recent advances in tau-based drug discovery, with an emphasis on the identification of compounds that inhibit the assembly of tau into multimers and fibrils...
  4. pmc Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies
    Kurt 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
    ..Here, we focus on strategies directed at reducing misfolded tau and compensating for the loss of normal tau function...
  5. pmc The characterization of microtubule-stabilizing drugs as possible therapeutic agents for Alzheimer's disease and related tauopathies
    Kurt R Brunden
    Center for Neurodegenerative Disease Research and Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
    Pharmacol Res 63:341-51. 2011
    ....
  6. pmc 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
    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. 2012
    ..These 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...
  7. doi request reprint Aminothienopyridazine inhibitors of tau aggregation: evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties
    Carlo Ballatore
    Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104 6323, USA
    Bioorg Med Chem 20:4451-61. 2012
    ..The latter studies revealed that this compound is well-tolerated with no notable side-effects at an oral dose of 50mg/kg/day...
  8. pmc Discovery of brain-penetrant, orally bioavailable aminothienopyridazine inhibitors of tau aggregation
    Carlo Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, USA
    J Med Chem 53:3739-47. 2010
    ..Taken together, these results suggest that examples from the ATPZ class hold promise as candidates for in vivo efficacy studies in animal models of neurodegenerative tauopathies...
  9. pmc Aminothienopyridazines and methylene blue affect Tau fibrillization via cysteine oxidation
    Alex Crowe
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 288:11024-37. 2013
    ..These findings reveal that the ATPZs and methylene blue act by a mechanism that may affect their viability as potential therapeutic agents...
  10. pmc Microtubule stabilizing agents as potential treatment for Alzheimer's disease and related neurodegenerative tauopathies
    Carlo Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, United States
    J Med Chem 55:8979-96. 2012
    ....
  11. pmc Brain-penetrant tetrahydronaphthalene thromboxane A2-prostanoid (TP) receptor antagonists as prototype therapeutics for Alzheimer's disease
    James H Soper
    Center for Neurodegenerative Disease Research, Institute on Aging, Perlman School of Medicine, University of Pennsylvania, 3600 Spruce Street, Philadelphia, Pennsylvania, 19104 6323
    ACS Chem Neurosci 3:928-40. 2012
    ..Compounds of this type hold promise as potential lead structures to develop drug candidates for the treatment of AD...
  12. pmc Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets
    Virginia M Y Lee
    Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cold Spring Harb Perspect Med 1:a006437. 2011
    ..Finally, we discuss the challenges and potential benefits of tau-directed drug discovery programs...
  13. pmc 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
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, School of Medicine and Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 31:14436-49. 2011
    ..These studies also implicate CRF in AD pathophysiology and suggest that pharmacological manipulation of this neuropeptide may be a potential therapeutic strategy for AD...
  14. pmc Characterization of tau fibrillization in vitro
    Shaohua Xu
    The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, USA
    Alzheimers Dement 6:110-7. 2010
    ..By using recombinant human tau, we have delineated events leading to the conversion of normal soluble tau into tau fibrils...
  15. pmc Lewy body-like α-synuclein aggregates resist degradation and impair macroautophagy
    Selcuk A Tanik
    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 288:15194-210. 2013
    ..Importantly, we also find that α-syn aggregates impair overall macroautophagy by reducing autophagosome clearance, which may contribute to the increased cell death that is observed in aggregate-bearing cells...
  16. pmc A model for improving the treatment and care of Alzheimer's disease patients through interdisciplinary research
    John Q Trojanowski
    Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA
    Alzheimers Dement 8:564-73. 2012
    ..The "Ware-UPenn" program has been presented in this report as a useful prototype for partnerships between private philanthropy and academia in planning and developing programs to address a major national public health problem...
  17. pmc Effects of TNFalpha-converting enzyme inhibition on amyloid beta production and APP processing in vitro and in vivo
    Minkyu L Kim
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 28:12052-61. 2008
    ..Accordingly, it is possible that TACE inhibitors could reduce TNFalpha levels without increasing Abeta levels within the AD brain...
  18. doi request reprint Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497
    Carlo Ballatore
    University of Pennsylvania, Perelman School of Medicine, Center for Neurodegenerative Disease Research, 3600 Spruce Street, Philadelphia, PA 19104 6323, USA
    Expert Opin Ther Pat 24:355-60. 2014
    ..Moreover, examples of this class of compounds exhibit absorption, distribution, metabolism, excretion and pharmacokinetics (ADME-PK) properties that are appropriate for CNS PET ligands. ..
  19. pmc Cyclopentane-1,3-dione: a novel isostere for the carboxylic acid functional group. Application to the design of potent thromboxane (A2) receptor antagonists
    Carlo Ballatore
    Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104 6323, United States
    J Med Chem 54:6969-83. 2011
    ..Given the combination of the relatively strong acidity, tunable lipophilicity, and versatility of the structure, the cyclopentane-1,3-dione moiety may constitute a valuable addition to the palette of carboxylic acid isosteres...
  20. pmc Identification of aminothienopyridazine inhibitors of tau assembly by quantitative high-throughput screening
    Alex Crowe
    Center for Neurodegenerative Disease Research, Institute on Aging, and Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 48:7732-45. 2009
    ..Thus, the ATPZ molecules described here represent a novel class of tau assembly inhibitors that merit further development for testing in animal models of AD-like tau pathology...
  21. pmc Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells
    Kelvin C Luk
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, Philadelphia, PA 19104 4283, USA
    Proc Natl Acad Sci U S A 106:20051-6. 2009
    ....
  22. pmc Evidence that non-fibrillar tau causes pathology linked to neurodegeneration and behavioral impairments
    Kurt R Brunden
    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Alzheimers Dis 14:393-9. 2008
    ....
  23. pmc Advancing Alzheimer's disease diagnosis, treatment, and care: recommendations from the Ware Invitational Summit
    Mary D Naylor
    Institute on Aging, University of Pennsylvania, Philadelphia, USA
    Alzheimers Dement 8:445-52. 2012
    ..The workgroups shared, discussed, and compiled an integrated set of priorities, recommendations, and action plans, which are presented in this article...