Stuart Lipton

Summary

Affiliation: The Burnham Institute
Country: USA

Publications

  1. ncbi request reprint Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation
    Stuart A Lipton
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Trends Neurosci 25:474-80. 2002
  2. pmc Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin
    Shu ichi Okamoto
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA
    Nat Med 15:1407-13. 2009
  3. pmc NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration
    Young Don Kwak
    Department of Pharmacology, University of Tennessee Health Science Center, College of Medicine, 874 Union Avenue, Memphis TN, 38163, USA
    Mol Neurodegener 5:49. 2010
  4. pmc Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety
    Kun Xia
    State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China
    Mol Brain 3:23. 2010
  5. pmc Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer's and Parkinson's diseases
    Tomohiro Nakamura
    Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Apoptosis 15:1354-63. 2010
  6. ncbi request reprint Comment on "S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function"
    Stuart A Lipton
    Center for Neuroscience and Aging, Burnham Institute, La Jolla, CA 92037, USA
    Science 308:1870; author reply 1870. 2005
  7. ncbi request reprint The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism
    Stuart A Lipton
    The Burnham Institute, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Alzheimer Res 2:155-65. 2005
  8. pmc Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults
    Stuart A Lipton
    The Burnham Institute, and the University of California, San Diego, La Jolla, California 92037, USA
    NeuroRx 1:101-10. 2004
  9. ncbi request reprint Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond
    Stuart A Lipton
    Burnham Institute for Medical Research, University of California at San Diego, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Drug Discov 5:160-70. 2006
  10. ncbi request reprint Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation
    Stuart A Lipton
    The Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Drug Targets 8:621-32. 2007

Research Grants

Detail Information

Publications78

  1. ncbi request reprint Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation
    Stuart A Lipton
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Trends Neurosci 25:474-80. 2002
    ..This article reviews the basis for these molecular cysteine switches, drawing on the NMDA receptor as an exemplary protein, and proposes a molecular model for the action of S-nitrosylation based on recently derived crystal structures...
  2. pmc Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin
    Shu ichi Okamoto
    Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA
    Nat Med 15:1407-13. 2009
    ..Our findings offer a rational therapeutic approach for protecting susceptible neurons in Huntington's disease...
  3. pmc NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration
    Young Don Kwak
    Department of Pharmacology, University of Tennessee Health Science Center, College of Medicine, 874 Union Avenue, Memphis TN, 38163, USA
    Mol Neurodegener 5:49. 2010
    ..However the molecular signals and mechanism underlying PTEN loss are unknown...
  4. pmc Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxiety
    Kun Xia
    State Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan 410078, China
    Mol Brain 3:23. 2010
    ..Our study suggests that KChIP1 is a synaptic protein that regulates behavioral anxiety by modulating inhibitory synaptic transmission, and drugs that act on KChIP1 may help to treat patients with mood disorders including anxiety...
  5. pmc Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer's and Parkinson's diseases
    Tomohiro Nakamura
    Center for Neuroscience, Aging, and Stem Cell Research, Sanford Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Apoptosis 15:1354-63. 2010
    ..For example, S-nitrosylation of parkin disrupts its E3 ubiquitin ligase activity, and thereby affects Lewy body formation and neuronal cell death...
  6. ncbi request reprint Comment on "S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function"
    Stuart A Lipton
    Center for Neuroscience and Aging, Burnham Institute, La Jolla, CA 92037, USA
    Science 308:1870; author reply 1870. 2005
  7. ncbi request reprint The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism
    Stuart A Lipton
    The Burnham Institute, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Alzheimer Res 2:155-65. 2005
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  8. pmc Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults
    Stuart A Lipton
    The Burnham Institute, and the University of California, San Diego, La Jolla, California 92037, USA
    NeuroRx 1:101-10. 2004
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites, in addition to its ion channel, that could potentially be used for safe but effective clinical intervention...
  9. ncbi request reprint Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond
    Stuart A Lipton
    Burnham Institute for Medical Research, University of California at San Diego, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Rev Drug Discov 5:160-70. 2006
    ....
  10. ncbi request reprint Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation
    Stuart A Lipton
    The Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California San Diego, La Jolla, California 92037, USA
    Curr Drug Targets 8:621-32. 2007
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  11. ncbi request reprint Dueling activities of AIF in cell death versus survival: DNA binding and redox activity
    Stuart A Lipton
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Cell 111:147-50. 2002
    ..New evidence suggests, however, that a redox-active enzymatic region of AIF may be antiapoptotic while a DNA binding region is proapoptotic...
  12. ncbi request reprint Paradigm shift in NMDA receptor antagonist drug development: molecular mechanism of uncompetitive inhibition by memantine in the treatment of Alzheimer's disease and other neurologic disorders
    Stuart A Lipton
    The Scripps Research Institute, and the University of California, San Diego, La Jolla, CA 92037, USA
    J Alzheimers Dis 6:S61-74. 2004
    ..These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention...
  13. ncbi request reprint Pathologically activated therapeutics for neuroprotection
    Stuart A Lipton
    Burnham Institute for Medical Research, The Salk Institute for Biological Studies, The Scripps Research Institute, and the University of California at San Diego 10901 North Torrey Pines Road, La Jolla, California 29, 037, USA
    Nat Rev Neurosci 8:803-8. 2007
    ..This approach has already met with success, and has led to the development of the potentially neuroprotective drug memantine, an N-methyl-D-aspartate (NMDA)-type and glutamate receptor antagonist...
  14. ncbi request reprint HIV-1 infection and AIDS: consequences for the central nervous system
    M Kaul
    Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Death Differ 12:878-92. 2005
    ..This review will discuss recently uncovered pathologic neuroimmune and degenerative mechanisms contributing to neuronal damage induced by HIV-1 and potential approaches for development of future therapeutic intervention...
  15. ncbi request reprint HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection
    M Kaul
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell Death Differ 14:296-305. 2007
    ..This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization...
  16. ncbi request reprint Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietin
    M Kaul
    Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neurotox Res 8:167-86. 2005
    ..This review will discuss experimental and potentially future therapeutic strategies based on recently uncovered pathologic mechanisms contributing to neuronal damage induced by HIV-1...
  17. ncbi request reprint Pathways to neuronal injury and apoptosis in HIV-associated dementia
    M Kaul
    Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 410:988-94. 2001
    ..Recent advances in understanding the signalling pathways mediating these events offer hope for therapeutic intervention...
  18. ncbi request reprint Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades
    M Digicaylioglu
    Center for Neuroscience and Aging Research, The Burnham Institute, La Jolla, CA 92037, USA
    Nature 412:641-7. 2001
    ..Thus neuronal EPORs activate a neuroprotective pathway that is distinct from previously well characterized Jak and NF-kappaB functions. Moreover, this EPO effect may underlie neuroprotection mediated by hypoxic-ischaemic preconditioning...
  19. pmc Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation
    S Okamoto
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 97:7561-6. 2000
    ..These findings suggest that the p38alpha/MEF2 pathway prevents cell death during neuronal differentiation...
  20. pmc Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducers
    T Satoh
    Center for Neuroscience and Aging, The Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 103:768-73. 2006
    ..NEPPs thus represent a therapeutic approach for stroke and neurodegenerative disorders...
  21. ncbi request reprint Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neurons
    H Yuan
    Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell Death Differ 14:462-71. 2007
    ..Taken together, these data indicate that the mitochondrial fission machinery acts upstream of the Bcl-2 family of proteins in neurons challenged with nitrosative stress...
  22. ncbi request reprint Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseases
    T Nakamura
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA
    Cell Mol Life Sci 64:1609-20. 2007
    ..Here, we present evidence for the hypothesis that nitric oxide contributes to degenerative conditions by S-nitrosylating specific chaperones or UPS proteins that would otherwise prevent accumulation of misfolded proteins...
  23. pmc Molecular stages of rapid and uniform neuralization of human embryonic stem cells
    R Bajpai
    Neuroscience, Aging, and Stem Cell Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell Death Differ 16:807-25. 2009
    ..In conclusion, our study provides a framework for future analysis of molecular signaling during ESC neuralization...
  24. ncbi request reprint Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptor
    J M Sullivan
    Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California 92037
    Neuron 13:929-36. 1994
    ..Redox modulation of heteromeric NR1-NR2A receptors appeared to be different from that of the other heteromeric receptors, indicating the presence of one or more unique redox modulatory sites on NR1-NR2A receptors...
  25. ncbi request reprint Three pairs of cysteine residues mediate both redox and zn2+ modulation of the nmda receptor
    Y Choi
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    J Neurosci 21:392-400. 2001
    ..Thus, these cysteine residues do not appear to coordinate Zn(2+) directly. Instead, the redox status of these cysteine residues may modulate the sensitivity of the receptor to Zn(2+)...
  26. ncbi request reprint Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disorders
    Stuart A Lipton
    Neuroscience and Aging Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    Int Rev Neurobiol 82:1-27. 2007
    ..Targeted S-nitrosylation of the NMDA receptor can be achieved by coupling NO to memantine, yielding second-generation "UFO drugs" known as NitroMemantines...
  27. ncbi request reprint Caspase cascades in human immunodeficiency virus-associated neurodegeneration
    Gwenn A Garden
    Department of Neurology, University of Washington, Seattle, Washington 98195, USA
    J Neurosci 22:4015-24. 2002
    ..These findings suggest that pharmacologic interventions aimed at the caspase enzyme pathways may be beneficial for the prevention or treatment of HAD...
  28. ncbi request reprint Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study
    Giovanni Schifitto
    University of Rochester, Rochester, New York 14620, USA
    AIDS 21:1877-86. 2007
    ..To assess the safety and efficacy of memantine, an uncompetitive antagonist of the N-methyl-D-aspartate receptor as treatment of HIV-associated cognitive impairment...
  29. ncbi request reprint S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death
    Zezong Gu
    Center for Neuroscience and Aging, Program in Cell Adhesion and Extracellular Matrix Biology, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 297:1186-90. 2002
    ..These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity...
  30. pmc Takusan: a large gene family that regulates synaptic activity
    Shichun Tu
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Neuron 55:69-85. 2007
    ..Conversely, treating cultured neurons with RNAi targeting alpha-takusan variants resulted in the opposite phenotype. Hence, alpha-takusan represents a large gene family that regulates synaptic activity...
  31. pmc Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells
    D Eugene Redmond
    Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA
    Proc Natl Acad Sci U S A 104:12175-80. 2007
    ..We propose that multiple modes of reciprocal interaction between exogenous hNSCs and the pathological host milieu underlie the functional improvement observed in this model of PD...
  32. ncbi request reprint Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiation
    Shu ichi Okamoto
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Brain Res Mol Brain Res 107:89-96. 2002
    ..These findings suggest that SP1 and MAZ mediate enhancement of NR1 promoter activity during neuronal differentiation despite the fact that their binding activity does not change...
  33. ncbi request reprint Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the rat retina
    Shin Ichi Manabe
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Invest Ophthalmol Vis Sci 44:385-92. 2003
    ....
  34. ncbi request reprint Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseases
    Tomohiro Nakamura
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Aging Cell 6:351-9. 2007
    ..Here, we present evidence for the hypothesis that NO contributes to normal brain aging and degenerative conditions by S-nitrosylating specific chaperones that would otherwise prevent accumulation of misfolded proteins...
  35. ncbi request reprint Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines
    Won Tak Choi
    Department of Biochemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    J Biol Chem 282:7154-63. 2007
    ....
  36. pmc Hypoxia enhances S-nitrosylation-mediated NMDA receptor inhibition via a thiol oxygen sensor motif
    Hiroto Takahashi
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuron 53:53-64. 2007
    ..These thiols may be nitrosylated preferentially during increasing hypoxia or stroke conditions, thus preventing excessive activity associated with cytotoxicity while avoiding blockade of physiologically active NMDARs...
  37. ncbi request reprint Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons
    Mehrdad Alirezaei
    Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci 27:11047-55. 2007
    ..Together, these results identify PKR as a critical mediator of gp120 neurotoxicity, suggesting that activation of PKR contributes to the neuronal injury and cell death observed in HAD...
  38. ncbi request reprint Emerging roles of S-nitrosylation in protein misfolding and neurodegenerative diseases
    Tomohiro Nakamura
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92039, USA
    Antioxid Redox Signal 10:87-101. 2008
    ....
  39. pmc A Golgi fragmentation pathway in neurodegeneration
    Saya Nakagomi
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neurobiol Dis 29:221-31. 2008
    ..Taken together, these findings implicate the Golgi as a sensor of stress signals in cell death pathways...
  40. ncbi request reprint Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits
    Jon E Chatterton
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 415:793-8. 2002
    ..By itself, glycine is normally thought of as an inhibitory neurotransmitter. In contrast, these NR1/NR3A or -3B 'NMDARs' constitute a type of excitatory glycine receptor...
  41. pmc Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosis
    Shu ichi Okamoto
    Center for Neuroscience and Aging, Apoptosis and Cell Death Research Program, The Burnham Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 99:3974-9. 2002
    ..Additionally, we show that similar MEF2 cleavage fragments are generated in vivo during focal stroke damage. Hence, this pathway appears to have pathophysiological relevance in vivo...
  42. ncbi request reprint Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons
    Yasnory F Sasaki
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    J Neurophysiol 87:2052-63. 2002
    ..Finally, a new longer splice variant of NR3A has been cloned and found to be expressed in rodent cortical neurons by single-cell RT-PCR and in situ hybridization...
  43. pmc Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo
    Hao Li
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 105:9397-402. 2008
    ..Our data support a crucial role for MEF2C in programming early neuronal differentiation and proper distribution within the layers of the neocortex...
  44. pmc Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells
    Zhen Li
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 28:6557-68. 2008
    ....
  45. doi request reprint HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrest
    Shu ichi Okamoto
    Center for Neuroscience, Stem Cells, and Aging, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Cell Stem Cell 1:230-6. 2007
    ..Our findings define a molecular mechanism that compromises adult neurogenesis in this neurodegenerative disorder...
  46. ncbi request reprint Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection and AIDS
    Marcus Kaul
    Center for Neuroscience and Aging Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    J Neuroimmune Pharmacol 1:138-51. 2006
    ..This article addresses recently uncovered pathologic neuroimmune and degenerative mechanisms contributing to neuronal damage induced by HIV-1 and discusses experimental and potentially future therapeutic approaches...
  47. pmc S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease
    Jianguo Fang
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:18742-7. 2007
    ..Dopaminergic neurons, which are lost in PD, become particularly vulnerable. Thus, our data provide a direct link between nitrosative/oxidative stress and neurodegenerative disorders such as PD...
  48. ncbi request reprint Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons
    Gary Tong
    Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurophysiol 99:122-32. 2008
    ..Taken together, these results show that NR3A subunits contribute to NMDAR responses from both synaptic and extrasynaptic receptors, likely composed of NR1, NR2, and NR3 subunits...
  49. ncbi request reprint Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1
    Takumi Satoh
    Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate, Japan
    J Neurochem 104:1116-31. 2008
    ....
  50. ncbi request reprint NR3A modulates the outer vestibule of the "NMDA" receptor channel
    Akira Wada
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92037, USA
    J Neurosci 26:13156-66. 2006
    ..This modified channel vestibule may also explain the dominant-negative effect of the NR3 subunit on channel behavior when coexpressed with NR1 and NR2 subunits...
  51. ncbi request reprint Redox regulation of neuronal survival mediated by electrophilic compounds
    Takumi Satoh
    Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020 8551, Japan
    Trends Neurosci 30:37-45. 2007
    ....
  52. ncbi request reprint Excitatory amino acid neurotoxicity
    Thomas Gillessen
    Institut fuer Pharmakologie und Toxikologie, Bereich Studien und Wissenachaft, Neuherbergstrasse 11, 80937 Muenchen, Germany
    Adv Exp Med Biol 513:3-40. 2002
  53. ncbi request reprint BAG1 over-expression in brain protects against stroke
    Pawel Kermer
    Department of Neurology, University of Goettingen, Germany
    Brain Pathol 13:495-506. 2003
    ....
  54. ncbi request reprint Pharmacological implications of two distinct mechanisms of interaction of memantine with N-methyl-D-aspartate-gated channels
    Huei Sheng Vincent Chen
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    J Pharmacol Exp Ther 314:961-71. 2005
    ..In the future, these parameters should be considered in searching for improved neuroprotective agents in this class...
  55. ncbi request reprint A developmental influence of the N-methyl-D-aspartate receptor NR3A subunit on prepulse inhibition of startle
    Suzanne A Brody
    Department of Neuroscience, University of California, San Diego, La Jolla 92093 0804, USA
    Biol Psychiatry 57:1147-52. 2005
    ..NR3A reduces NMDA current in native neurons expressing NR1 and NR2 subunits and forms glycine receptors when expressed with NR1 in the absence of NR2 in both oocyte and mammalian expression systems...
  56. ncbi request reprint Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channels
    Ella Bossy-Wetzel
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Neuron 41:351-65. 2004
    ..Thus, these data establish a new form of crosstalk between NO and Zn2+ apoptotic signal transduction pathways that may contribute to neurodegeneration...
  57. ncbi request reprint Signaling pathways to neuronal damage and apoptosis in human immunodeficiency virus type 1-associated dementia: Chemokine receptors, excitotoxicity, and beyond
    Marcus Kaul
    The Burnham Institute, Center for Neuroscience and Aging Research, La Jolla, California 92037, USA
    J Neurovirol 10:97-101. 2004
    ..This article discusses recently identified pathways to neuronal damage triggered by HIV-1 and efforts aimed at development of applicable therapeutic intervention...
  58. ncbi request reprint Mitochondrial fission in apoptosis, neurodegeneration and aging
    Ella Bossy-Wetzel
    Del E Webb Center for Neuroscience and Aging The Burnham Institute, 10901 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Curr Opin Cell Biol 15:706-16. 2003
    ..A shift in the rate of mitochondrial fission or fusion may provide a new mechanistic explanation for the mitochondrial dysfunction in neurodegenerative diseases and normal aging, and may offer a new target for therapeutic intervention...
  59. ncbi request reprint BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stress
    Han Jung Chae
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Mol Cell 15:355-66. 2004
    ..Thus, BI-1 regulates a cell death pathway important for cytopreservation during ER stress...
  60. ncbi request reprint Molecular pathways to neurodegeneration
    Ella Bossy-Wetzel
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nat Med 10:S2-9. 2004
    ....
  61. pmc Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity
    Dongdong Yao
    Center for Neuroscience and Aging, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:10810-4. 2004
    ..These findings may thus provide a molecular link between free radical toxicity and protein accumulation in sporadic Parkinson's disease...
  62. pmc Acute neuroprotective synergy of erythropoietin and insulin-like growth factor I
    Murat Digicaylioglu
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:9855-60. 2004
    ..These results imply that EPO+IGF-I exert cooperative actions that afford acute neuroprotection via activation of the PI3-K-Akt pathway...
  63. ncbi request reprint Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damage
    Murat Digicaylioglu
    Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Neuroreport 15:761-3. 2004
    ..Here we show that EPO protects cerebrocortical neurons against apoptosis induced by HIV-1/gp120...
  64. ncbi request reprint Turning down, but not off
    Stuart A Lipton
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    Nature 428:473. 2004
  65. ncbi request reprint The chemical biology of clinically tolerated NMDA receptor antagonists
    Huei Sheng Vincent Chen
    Burnham Institute for Medical Research and the University of California San Diego, La Jolla, California 92037, USA
    J Neurochem 97:1611-26. 2006
    ..These second-generation memantine derivatives are designed as pathologically activated therapeutics, and in preliminary studies appear to have even greater neuroprotective properties than memantine...
  66. ncbi request reprint Mechanisms of neuronal injury and death in HIV-1 associated dementia
    Marcus Kaul
    Center for Neuroscience and Aging Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Curr HIV Res 4:307-18. 2006
    ..This article will review recently identified injurious mechanisms potentially contributing to neuronal death in association with HIV-1 disease and discuss recent and prospective approaches for therapy and prevention of HAD...
  67. pmc Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retina
    Xiaohong Fan
    OncoDevelopmental Biology Program Center for Neuroscience and Aging, Burnham Institute, La Jolla, California 92037, USA
    Mol Cell Biol 23:4637-48. 2003
    ..Our findings suggest that RA signaling may be necessary only during early stages of retina development and that if RA synthesis is needed in dorsal retina, it is catalyzed by multiple enzymes, including Raldh1...
  68. pmc Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons
    Mark J Barsoum
    Apoptosis and Cell Death Program, Burnham Institute for Medical Research, La Jolla, CA, USA
    EMBO J 25:3900-11. 2006
    ..Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A). Thus, persistent mitochondrial fission may play a causal role in NO-mediated neurotoxicity...
  69. ncbi request reprint S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
    Takashi Uehara
    Center for Neuroscience and Aging, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA
    Nature 441:513-7. 2006
    ..Thus, PDI prevents neurotoxicity associated with ER stress and protein misfolding, but NO blocks this protective effect in neurodegenerative disorders through the S-nitrosylation of PDI...
  70. ncbi request reprint Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior
    Guoqing Sheng
    Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Atlanta, Georgia 30322, USA
    Nat Med 12:526-33. 2006
    ..These findings provide evidence linking hypothalamic Hap1 to GABA in the stimulation of feeding and suggest that this mechanism is involved in the feeding-inhibitory actions of insulin in the brain...
  71. ncbi request reprint GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2
    Chunmei Zhao
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 278:34641-53. 2003
    ....
  72. ncbi request reprint N-methyl-D-aspartate receptor subunit NR3A in the retina: developmental expression, cellular localization, and functional aspects
    Nikolaus J Sucher
    Department of Biology and Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China
    Invest Ophthalmol Vis Sci 44:4451-6. 2003
    ..The present study is the first to investigate the expression and cellular localization of NR3A on the protein level in the retina and to elucidate its putative functional roles within the retinal circuitry...
  73. ncbi request reprint Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylation
    Ping Han
    Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
    J Neurosci 25:11542-52. 2005
    ..We suggest that CDK5 activation, through a calcium/calpain/p25 pathway, plays a key role in neuronal excitotoxicity and represents an underlying mechanism for the physiological functions of APP...
  74. ncbi request reprint Subunit-specific roles of glycine-binding domains in activation of NR1/NR3 N-methyl-D-aspartate receptors
    Marc Awobuluyi
    Burnham Institute for Medical Research, 10901 N Torrey Pines Rd, La Jolla, CA 92037, USA
    Mol Pharmacol 71:112-22. 2007
    ..NR3 subunits thus induce plasticity in NR1 with respect to subunit assembly and ligand binding/channel coupling that is unique among ligand-gated ion channel subunits...
  75. ncbi request reprint The pharmacology of aminoadamantane nitrates
    Yuqiang Wang
    NeuroMolecular Pharmaceuticals, Inc, 1050 Powell St, Emeryville, CA 94608, USA
    Curr Alzheimer Res 3:201-4. 2006
    ..The results also provide guidance for the synthesis of additional compounds that are likely to have the properties that are being sought...
  76. pmc Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cells
    Jinjuan Cui
    Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA
    J Physiol 553:895-909. 2003
    ..This study provides evidence for the existence of functional glycinergic synaptic input at the axon terminals of RBCs, suggesting that glycine receptors may play a role in modulating bipolar cell synaptic transmission...
  77. ncbi request reprint Sporadic ALS: blame it on the editor
    Stuart A Lipton
    Nat Med 10:347. 2004
  78. ncbi request reprint White matter NMDA receptors: an unexpected new therapeutic target?
    Peter K Stys
    Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, AB, T2N 4N1, Canada
    Trends Pharmacol Sci 28:561-6. 2007
    ....

Research Grants46

  1. RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS
    Stuart A Lipton; Fiscal Year: 2010
    ..To characterize the ligand-binding site of NR3-containing receptors, and use information from [2] and [3] to distinguish expression of NR1/NR3 "doublet" receptors from NR1/NR2/NR3 "triplet" receptors on RGCs. ..
  2. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2005
    ....
  3. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2004
    ....
  4. EPO PLUS IGF-I IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2006
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  5. Chemokines and Macrophages in HIV Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2003
    ..Neuronal apoptosis due to gp120 or chemokines will be monitored using several approaches. ..
  6. S-Nitrosylation of Matrix Metalloproteinases in AIDS
    Stuart Lipton; Fiscal Year: 2004
    ..In the future, the work proposed here may lead to new therapeutic targets based on the novel extracellular signaling pathway involving NO-related molecules and the MMPs that will be studied. ..
  7. RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2007
    ..To characterize the ligand-binding site of NR3-containing receptors, and use information from [2] and [3] to distinguish expression of NR1/NR3 "doublet" receptors from NR1/NR2/NR3 "triplet" receptors on RGCs. ..
  8. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2004
    ....
  9. RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2002
    ..3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second NMDAR subunit, NR3B, isolated from the rat retina. ..
  10. S-Nitrosylation of Matrix Metalloproteinases in AIDS
    Stuart Lipton; Fiscal Year: 2005
    ..In the future, the work proposed here may lead to new therapeutic targets based on the novel extracellular signaling pathway involving NO-related molecules and the MMPs that will be studied. ..
  11. RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2001
    ..3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second NMDAR subunit, NR3B, isolated from the rat retina. ..
  12. RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2004
    ..3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second NMDAR subunit, NR3B, isolated from the rat retina. ..
  13. La Jolla Interdisciplinary Neuroscience Center Cores
    Stuart Lipton; Fiscal Year: 2007
    ....
  14. AIDS-RELATED NEUROTOXCITY: GP120 AND CHEMOKINES
    Stuart Lipton; Fiscal Year: 2003
    ..5. Use neuronal cultures derived from CXCR4- and CCR5 knockout mice to assess the necessity of these receptors on in vitro gp120-induced toxicity. ..
  15. AIDS-RELATED NEUROTOXCITY: GP120 AND CHEMOKINES
    Stuart Lipton; Fiscal Year: 2001
    ..5. Use neuronal cultures derived from CXCR4- and CCR5 knockout mice to assess the necessity of these receptors on in vitro gp120-induced toxicity. ..
  16. Chemokines and Macrophages in HIV Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2001
    ..Neuronal apoptosis due to gp120 or chemokines will be monitored using several approaches. ..
  17. RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2000
    ..3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second NMDAR subunit, NR3B, isolated from the rat retina. ..
  18. AIDS-Related Neurotoxicity and Novel NMDAR Antagonists
    Stuart Lipton; Fiscal Year: 2006
    ..It is anticipated that these preclinical studies investigating the role of the NMDAR in neuronal cell injury may lead to new treatments for the neurological manifestations of AIDS. ..
  19. EPO PLUS IGF-IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2004
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  20. Erythropoietin PLUS IGF-IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2007
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  21. S-Nitrosylation of Matrix Metalloproteinases in AIDS
    Stuart Lipton; Fiscal Year: 2006
    ..In the future, the work proposed here may lead to new therapeutic targets based on the novel extracellular signaling pathway involving NO-related molecules and the MMPs that will be studied. ..
  22. Erythropoietin PLUS IGF-IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2009
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  23. AIDS-Related Neurotoxicity and Novel NMDAR Antagonists
    Stuart Lipton; Fiscal Year: 2009
    ..It is anticipated that these preclinical studies investigating the role of the NMDAR in neuronal cell injury may lead to new treatments for the neurological manifestations of AIDS. ..
  24. AIDS-Related Neurotoxicity and Novel NMDAR Antagonists
    Stuart Lipton; Fiscal Year: 2007
    ..It is anticipated that these preclinical studies investigating the role of the NMDAR in neuronal cell injury may lead to new treatments for the neurological manifestations of AIDS. ..
  25. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2003
    ....
  26. RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2003
    ..3] To elucidate the molecular mechanism of action of NR3A whereby it decreases NMDAR-activated current. [4] To clone and characterize a second NMDAR subunit, NR3B, isolated from the rat retina. ..
  27. Chemokines and Macrophages in HIV Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2002
    ..Neuronal apoptosis due to gp120 or chemokines will be monitored using several approaches. ..
  28. RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2006
    ..To characterize the ligand-binding site of NR3-containing receptors, and use information from [2] and [3] to distinguish expression of NR1/NR3 "doublet" receptors from NR1/NR2/NR3 "triplet" receptors on RGCs. ..
  29. EPO PLUS IGF-I IN NEUROPROTECTION FROM AIDS
    Stuart Lipton; Fiscal Year: 2005
    ..Hypothesis Tested: EPO+IGF-I act synergistically to activate the anti-apoptotic PI3 kinase/Akt signaling pathway, and thus provide a synergistic degree of neuroprotection. ..
  30. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2003
    ....
  31. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2002
    ....
  32. AIDS-Related Neurotoxicity and Novel NMDAR Antagonists
    Stuart Lipton; Fiscal Year: 2005
    ..It is anticipated that these preclinical studies investigating the role of the NMDAR in neuronal cell injury may lead to new treatments for the neurological manifestations of AIDS. ..
  33. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2006
    ....
  34. Caspase Cleavage of MEF2 Mediates Neuronal Apoptosis
    Stuart Lipton; Fiscal Year: 2007
    ....
  35. RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERS
    Stuart Lipton; Fiscal Year: 2009
    ..To characterize the ligand-binding site of NR3-containing receptors, and use information from [2] and [3] to distinguish expression of NR1/NR3 "doublet" receptors from NR1/NR2/NR3 "triplet" receptors on RGCs. ..
  36. ERYTHROPOIETIN-INDUCED NEUROPROTECTION
    Stuart Lipton; Fiscal Year: 2005
    ....
  37. AIDS-RELATED NEUROTOXCITY: GP120 AND CHEMOKINES
    Stuart Lipton; Fiscal Year: 2002
    ..5. Use neuronal cultures derived from CXCR4- and CCR5 knockout mice to assess the necessity of these receptors on in vitro gp120-induced toxicity. ..
  38. AIDS-RELATED NEUROTOXCITY: GP120 AND CHEMOKINES
    Stuart Lipton; Fiscal Year: 2000
    ..5. Use neuronal cultures derived from CXCR4- and CCR5 knockout mice to assess the necessity of these receptors on in vitro gp120-induced toxicity. ..
  39. S-Nitrosylation of Matrix Metalloproteinases in AIDS
    Stuart Lipton; Fiscal Year: 2007
    ..In the future, the work proposed here may lead to new therapeutic targets based on the novel extracellular signaling pathway involving NO-related molecules and the MMPs that will be studied. ..