Linda J Van Eldik

Summary

Affiliation: Northwestern University
Country: USA

Publications

  1. ncbi Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38
    Zhong Xie
    Department of Cell and Molecular Biology, and Drug Discovery Program, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60612, USA
    Glia 45:170-9. 2004
  2. pmc MFG-E8 regulates microglial phagocytosis of apoptotic neurons
    Abby D Fuller
    Department of Cell and Molecular Biology, Center for Drug Discovery and Chemical Biology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611, USA
    J Neuroimmune Pharmacol 3:246-56. 2008
  3. ncbi Barriers to Alzheimer disease drug discovery and development in academia
    Linda J Van Eldik
    Department of Cell and Molecular Biology, Northwestern Drug Discovery Program, Northwestern University Medical School, Chicago, Illinois 06011 3008, USA
    Alzheimer Dis Assoc Disord 16:S18-28. 2002
  4. ncbi Structure and enzymology of a death-associated protein kinase
    Linda J Van Eldik
    Drug Discovery Program and Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago IL 60611, USA
    Trends Pharmacol Sci 23:302-4. 2002
  5. ncbi The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain
    Linda J Van Eldik
    Northwestern Drug Discovery Program, and Department of Cell and Molecular Biology, Northwestern University Feinberg Medical School, Chicago IL 60611 3008, USA
    Restor Neurol Neurosci 21:97-108. 2003
  6. ncbi Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production
    Seon H Kim
    Drug Discovery Program, Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 4 202, Chicago, IL 60611 3008, USA
    Neurobiol Aging 25:431-9. 2004
  7. ncbi Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration
    Hantamalala Ralay Ranaivo
    Center for Drug Discovery and Chemical Biology, Chicago, Illinois 60611, USA
    J Neurosci 26:662-70. 2006
  8. pmc A novel p38 alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model
    Lenka Munoz
    Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E Chicago Ave, Mailcode W896, Chicago, IL 60611, USA
    J Neuroinflammation 4:21. 2007
  9. pmc Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits
    Wenhui Hu
    Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E Chicago Avenue, Mail Code W896, Chicago, IL 60611, USA
    Bioorg Med Chem Lett 17:414-8. 2007
  10. ncbi Enhanced susceptibility of S-100B transgenic mice to neuroinflammation and neuronal dysfunction induced by intracerebroventricular infusion of human beta-amyloid
    Jeffrey M Craft
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, Illinois 60611 3008, USA
    Glia 51:209-16. 2005

Research Grants

Collaborators

Detail Information

Publications33

  1. ncbi Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38
    Zhong Xie
    Department of Cell and Molecular Biology, and Drug Discovery Program, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60612, USA
    Glia 45:170-9. 2004
    ..These results show that p38 and JNK MAPKs, but not ERK1/2 MAPK, are important signal transduction pathways contributing to glia-induced neuron death...
  2. pmc MFG-E8 regulates microglial phagocytosis of apoptotic neurons
    Abby D Fuller
    Department of Cell and Molecular Biology, Center for Drug Discovery and Chemical Biology, Northwestern University Feinberg School of Medicine, 303 E Chicago Ave, Chicago, IL 60611, USA
    J Neuroimmune Pharmacol 3:246-56. 2008
    ..Our data suggest that MFG-E8 acts in the brain via microglia to aid in clearance of apoptotic neurons, and we hypothesize that a dysregulation of this process may be involved in neurodegenerative disease...
  3. ncbi Barriers to Alzheimer disease drug discovery and development in academia
    Linda J Van Eldik
    Department of Cell and Molecular Biology, Northwestern Drug Discovery Program, Northwestern University Medical School, Chicago, Illinois 06011 3008, USA
    Alzheimer Dis Assoc Disord 16:S18-28. 2002
    ....
  4. ncbi Structure and enzymology of a death-associated protein kinase
    Linda J Van Eldik
    Drug Discovery Program and Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago IL 60611, USA
    Trends Pharmacol Sci 23:302-4. 2002
    ....
  5. ncbi The Janus face of glial-derived S100B: beneficial and detrimental functions in the brain
    Linda J Van Eldik
    Northwestern Drug Discovery Program, and Department of Cell and Molecular Biology, Northwestern University Feinberg Medical School, Chicago IL 60611 3008, USA
    Restor Neurol Neurosci 21:97-108. 2003
    ....
  6. ncbi Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 beta production
    Seon H Kim
    Drug Discovery Program, Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 4 202, Chicago, IL 60611 3008, USA
    Neurobiol Aging 25:431-9. 2004
    ..These data demonstrate that MAPK pathways are important for microglial IL-1beta production, and suggest that different glial activators use distinct sets of signaling pathways to induce the same disease-relevant end-point in microglia...
  7. ncbi Glia as a therapeutic target: selective suppression of human amyloid-beta-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration
    Hantamalala Ralay Ranaivo
    Center for Drug Discovery and Chemical Biology, Chicago, Illinois 60611, USA
    J Neurosci 26:662-70. 2006
    ....
  8. pmc A novel p38 alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model
    Lenka Munoz
    Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E Chicago Ave, Mailcode W896, Chicago, IL 60611, USA
    J Neuroinflammation 4:21. 2007
    ....
  9. pmc Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits
    Wenhui Hu
    Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E Chicago Avenue, Mail Code W896, Chicago, IL 60611, USA
    Bioorg Med Chem Lett 17:414-8. 2007
    ..The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders...
  10. ncbi Enhanced susceptibility of S-100B transgenic mice to neuroinflammation and neuronal dysfunction induced by intracerebroventricular infusion of human beta-amyloid
    Jeffrey M Craft
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, Illinois 60611 3008, USA
    Glia 51:209-16. 2005
    ..Our data are consistent with a model in which S-100B overexpression in AD enhances glial activation and leads to an augmented neuroinflammatory process that increases the severity of neuropathologic sequelae...
  11. pmc Enhanced microglial activation and proinflammatory cytokine upregulation are linked to increased susceptibility to seizures and neurologic injury in a 'two-hit' seizure model
    Kathleen C Somera-Molina
    Integrated Graduate Program, Northwestern University, Chicago, IL, USA
    Brain Res 1282:162-72. 2009
    ....
  12. ncbi Glial activation links early-life seizures and long-term neurologic dysfunction: evidence using a small molecule inhibitor of proinflammatory cytokine upregulation
    Kathleen C Somera-Molina
    Integrated Graduate Program, Department of Pediatrics, Division of Neurology, Center for Drug Discovery and Chemical Biology, Northwestern Univrsity, Chicago, Illinois, USA
    Epilepsia 48:1785-800. 2007
    ....
  13. ncbi Human amyloid beta-induced neuroinflammation is an early event in neurodegeneration
    Jeffrey M Craft
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, Illinois 60611, USA
    Glia 53:484-90. 2006
    ....
  14. ncbi De novo and molecular target-independent discovery of orally bioavailable lead compounds for neurological disorders
    Laura K Wing
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, IL, USA
    Curr Alzheimer Res 3:205-14. 2006
    ..For the AD case study, novel lead compounds were developed in less than two years by a small academic group, and corporate sponsored clinical trials are planned...
  15. ncbi Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches
    Linda J Van Eldik
    Center for Drug Discovery and Chemical Biology, Northwestern University Chicago, Illinois 60611, USA
    Int Rev Neurobiol 82:277-96. 2007
    ....
  16. ncbi Discovery of a new class of synthetic protein kinase inhibitors that suppress selective aspects of glial activation and protect against beta-amyloid induced injury: a foundation for future medicinal chemistry efforts focused on targeting Alzheimer's disea
    D Martin Watterson
    Drug Discovery Program and Department of Molecular Pharmacology, Northwestern University Medical School, Chicago IL 60611, USA
    J Mol Neurosci 20:411-23. 2003
    ..Feasibility studies indicate their potential utility in current medicinal chemistry efforts focused on improvement in molecular properties and the longer term targeting of AD-related pathogenic processes...
  17. ncbi Aminopyridazines attenuate hippocampus-dependent behavioral deficits induced by human beta-amyloid in a murine model of neuroinflammation
    Jeffrey M Craft
    Drug Discovery Program, Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    J Mol Neurosci 24:115-22. 2004
    ....
  18. pmc Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury
    Eric Lloyd
    Division of Critical Care, Department of Pediatrics, Children s Memorial Hospital, 2300 Children s Plaza, Chicago, IL 60614, USA
    J Neuroinflammation 5:28. 2008
    ....
  19. ncbi Increased susceptibility of S100B transgenic mice to perinatal hypoxia-ischemia
    Mark S Wainwright
    Department of Pediatrics, Division of Neurology, Children s Memorial Hospital, Chicago, IL, USA
    Ann Neurol 56:61-7. 2004
    ..This is the first demonstration to our knowledge that overexpression of S100B in vivo enhances pathological response to injury...
  20. ncbi Aminopyridazines inhibit beta-amyloid-induced glial activation and neuronal damage in vivo
    Jeffrey M Craft
    Drug Discovery Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
    Neurobiol Aging 25:1283-92. 2004
    ....
  21. pmc Targeting protein kinases in central nervous system disorders
    Laura K Chico
    Center for Molecular Innovation and Drug Discovery, Northwestern University, Chicago, Illinois 60611, USA
    Nat Rev Drug Discov 8:892-909. 2009
    ....
  22. pmc The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target
    Aaron S Borders
    Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, IL 60611, USA
    BMC Neurosci 9:S12. 2008
    ..Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders...
  23. ncbi Validation of the neuroinflammation cycle as a drug discovery target using integrative chemical biology and lead compound development with an Alzheimer's disease-related mouse model
    Wenhui Hu
    Center for Drug Discovery and Chemical Biology, Northwestern University Chicago, IL 60611, USA
    Curr Alzheimer Res 2:197-205. 2005
    ....
  24. pmc Inhibition of experimental autoimmune encephalomyelitis by a novel small molecular weight proinflammatory cytokine suppressing drug
    William J Karpus
    Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    J Neuroimmunol 203:73-8. 2008
    ..These results demonstrate the efficacy of a novel class of therapeutic molecules for CNS demyelinating disease...
  25. pmc MCP-1-deficient mice show reduced neuroinflammatory responses and increased peripheral inflammatory responses to peripheral endotoxin insult
    Wendy L Thompson
    Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611, USA
    J Neuroinflammation 5:35. 2008
    ..The chemokine MCP-1 is highly expressed during endotoxemia and although much is known about the importance of MCP-1 in peripheral inflammatory responses to LPS, information about MCP-1 and CNS responses to peripheral LPS is lacking...
  26. ncbi A dual role for apolipoprotein e in neuroinflammation: anti- and pro-inflammatory activity
    Ling Guo
    Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
    J Mol Neurosci 23:205-12. 2004
    ..In addition, the observation that apoE4 has more robust pro-inflammatory activity than apoE3 provides a mechanistic link between the APOE4 allele and AD, and suggests potential apoE-based therapeutic strategies...
  27. pmc Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK dependent pathways in rat astrocytes [corrected]
    Wendy L Thompson
    Department of Cell and Molecular Biology, and Center for Drug Discovery and Chemical Biology, Northwestern University, Chicago, IL 60611, USA
    Brain Res 1287:47-57. 2009
    ..In addition, our results suggest that CCL2 and CCL7 share similarities in the signaling pathways necessary for their upregulation...
  28. ncbi Discovery of new chemical classes of synthetic ligands that suppress neuroinflammatory responses
    D Martin Watterson
    Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago IL 60611 3008, USA
    J Mol Neurosci 19:89-93. 2002
    ..Therefore, the potential bioavailability of 3-AP derivatives and the demonstrated cellular selectivity demand that future research address the potential efficacy of selective 3-AP derivatives in animal models of disease...
  29. ncbi Neuroinflammation: a potential therapeutic target
    Jeffrey M Craft
    Center for Drug Discovery and Chemical Biology, Northwestern University, Feinberg School of Medicine, 303 E Chicago Avenue, Mail Code W 896, Chicago, IL 60611 3008, USA
    Expert Opin Ther Targets 9:887-900. 2005
    ..The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component...
  30. pmc Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo
    Daniel R Clayburgh
    Department of Pathology, The University of Chicago, Chicago, Illinois, USA
    J Clin Invest 115:2702-15. 2005
    ..The data also indicate that inhibition of epithelial MLCK may be an effective non-immunosuppressive therapy for treatment of immune-mediated intestinal disease...
  31. pmc Levels of soluble apolipoprotein E/amyloid-β (Aβ) complex are reduced and oligomeric Aβ increased with APOE4 and Alzheimer disease in a transgenic mouse model and human samples
    Leon M Tai
    Department of Anatomy and Cell Biology, University of Illinois, Chicago, Illinois 60612, USA
    J Biol Chem 288:5914-26. 2013
    ..Overall, apoE isoform-specific formation of soluble apoE/Aβ modulates oAβ levels, suggesting a basis for APOE4-induced AD risk and a mechanistic approach to AD biomarkers...
  32. pmc Protein kinase involved in lung injury susceptibility: evidence from enzyme isoform genetic knockout and in vivo inhibitor treatment
    Mark S Wainwright
    Departments of Pediatrics, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 100:6233-8. 2003
    ..These convergent results from two independent approaches demonstrate a pivotal in vivo role for MLCK in susceptibility to lung injury and validate MLCK as a potential drug discovery target for lung injury...
  33. pmc Early stage drug treatment that normalizes proinflammatory cytokine production attenuates synaptic dysfunction in a mouse model that exhibits age-dependent progression of Alzheimer's disease-related pathology
    Adam D Bachstetter
    Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536, USA
    J Neurosci 32:10201-10. 2012
    ....

Research Grants8

  1. Molecular mechanisms of Glial S100 in Neuroinflammation
    Linda Van Eldik; Fiscal Year: 2004
    ..These studies will provide new insight into glial-neuronal interactions and the knowledge base necessary for pursuit of novel strategies to block glial activation and its neurotoxic consequences. ..
  2. Drug Discovery Academic Research Experience(DARE)
    Linda Van Eldik; Fiscal Year: 2006
    ....
  3. DRUG DISCOVERY TRAINING IN AGE-RELATED DISORDERS
    Linda Van Eldik; Fiscal Year: 2007
    ..Our program addresses a national need and will produce outstanding scientists for the future that will be prepared to address and solve age-reIated disorders. ..
  4. Neuroinflammation in Alzheimers Disease Murine Models
    Jeffrey Craft; Fiscal Year: 2007
    ..These mice may then be treated with test compounds to identify and/or verify the neuroinflammatory pathways through which these agents exert their effects. ..