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Genomes and Genes | Stuart LiptonSummaryAffiliation: The Burnham Institute Country: USA Publications
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Publications
NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegenerationYoung 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...- Roles of KChIP1 in the regulation of GABA-mediated transmission and behavioral anxietyKun 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... - Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer's and Parkinson's diseasesTomohiro 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... - Cysteine regulation of protein function--as exemplified by NMDA-receptor modulationStuart 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... - 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 disordersStuart 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... - 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 - Pathologically activated therapeutics for neuroprotectionStuart 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... - The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonismStuart 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... - Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylationStuart 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... - 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 insultsStuart 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... - Dueling activities of AIF in cell death versus survival: DNA binding and redox activityStuart 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... - Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyondStuart 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.... - HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protectionM 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... - HIV-1 infection and AIDS: consequences for the central nervous systemM 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... - Experimental and potential future therapeutic approaches for HIV-1 associated dementia targeting receptors for chemokines, glutamate and erythropoietinM 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... - Pathways to neuronal injury and apoptosis in HIV-associated dementiaM 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... - Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascadesM 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... - Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiationS 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... - Molecular mechanisms of nitrosative stress-mediated protein misfolding in neurodegenerative diseasesT 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... - Mitochondrial fission is an upstream and required event for bax foci formation in response to nitric oxide in cortical neuronsH 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... - Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophilic [correction of electrophillic] phase II inducersT 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... - Molecular stages of rapid and uniform neuralization of human embryonic stem cellsR 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... - Identification of two cysteine residues that are required for redox modulation of the NMDA subtype of glutamate receptorJ 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... - Three pairs of cysteine residues mediate both redox and zn2+ modulation of the nmda receptorY 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+)... - Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neuronsMark 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... - Subunit-specific roles of glycine-binding domains in activation of NR1/NR3 N-methyl-D-aspartate receptorsMarc 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... - Hypoxia enhances S-nitrosylation-mediated NMDA receptor inhibition via a thiol oxygen sensor motifHiroto 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... - Takusan: a large gene family that regulates synaptic activityShichun 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... - NR3A modulates the outer vestibule of the "NMDA" receptor channelAkira 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... - Redox regulation of neuronal survival mediated by electrophilic compoundsTakumi Satoh
Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka 020 8551, Japan
Trends Neurosci 30:37-45. 2007.... - The pharmacology of aminoadamantane nitratesYuqiang 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... - Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokinesWon Tak Choi
Department of Biochemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
J Biol Chem 282:7154-63. 2007.... - Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cellsZhen 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.... - HIV/gp120 decreases adult neural progenitor cell proliferation via checkpoint kinase-mediated cell-cycle withdrawal and G1 arrestShu 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... - Mechanisms of neuroimmunity and neurodegeneration associated with HIV-1 infection and AIDSMarcus 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... - S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's diseaseJianguo 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... - Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neuronsGary 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... - 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 Keap1Takumi Satoh
Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate, Japan
J Neurochem 104:1116-31. 2008.... - A Golgi fragmentation pathway in neurodegenerationSaya 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... - Emerging roles of S-nitrosylation in protein misfolding and neurodegenerative diseasesTomohiro Nakamura
Center for Neuroscience and Aging, Burnham Institute for Medical Research, La Jolla, California 92039, USA
Antioxid Redox Signal 10:87-101. 2008.... - Human immunodeficiency virus-1/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neuronsMehrdad 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... - Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy studyGiovanni 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... - Inflammatory mediators leading to protein misfolding and uncompetitive/fast off-rate drug therapy for neurodegenerative disordersStuart 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... - Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cellsD 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... - Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseasesTomohiro 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... - Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivoHao 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... - Mechanisms of neuronal injury and death in HIV-1 associated dementiaMarcus 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... - BAG1 over-expression in brain protects against strokePawel Kermer
Department of Neurology, University of Goettingen, Germany
Brain Pathol 13:495-506. 2003.... - Mitochondrial fission in apoptosis, neurodegeneration and agingElla 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... - N-methyl-D-aspartate receptor subunit NR3A in the retina: developmental expression, cellular localization, and functional aspectsNikolaus 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... - GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2Chunmei Zhao
Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 278:34641-53. 2003.... - Targeted disruption of Aldh1a1 (Raldh1) provides evidence for a complex mechanism of retinoic acid synthesis in the developing retinaXiaohong 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... - Excitatory amino acid neurotoxicityThomas Gillessen
Institut fuer Pharmakologie und Toxikologie, Bereich Studien und Wissenachaft, Neuherbergstrasse 11, 80937 Muenchen, Germany
Adv Exp Med Biol 513:3-40. 2002 - Divergent NMDA signals leading to proapoptotic and antiapoptotic pathways in the rat retinaShin-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..These inhibitor studies suggest that the p38 MAP kinase pathway is proapoptotic, whereas the PI-3 kinase-Akt pathway is antiapoptotic in RGC death induced by NMDA... - Effect of the ubiquitous transcription factors, SP1 and MAZ, on NMDA receptor subunit type 1 (NR1) expression during neuronal differentiationShu-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... - S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell deathZezong 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... - Caspase cascades in human immunodeficiency virus-associated neurodegenerationGwenn 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... - Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neuronsYasnory 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... - Dominant-interfering forms of MEF2 generated by caspase cleavage contribute to NMDA-induced neuronal apoptosisShu 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... - Crosstalk between nitric oxide and zinc pathways to neuronal cell death involving mitochondrial dysfunction and p38-activated K+ channelsElla 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... - Signaling pathways to neuronal damage and apoptosis in human immunodeficiency virus type 1-associated dementia: Chemokine receptors, excitotoxicity, and beyondMarcus 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... - Excitatory glycine receptors containing the NR3 family of NMDA receptor subunitsJon 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... - The chemical biology of clinically tolerated NMDA receptor antagonistsHuei 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... - S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegenerationTakashi 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... - Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behaviorGuoqing 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... - Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylationPing 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... - Pharmacological implications of two distinct mechanisms of interaction of memantine with N-methyl-D-aspartate-gated channelsHuei 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... - A developmental influence of the N-methyl-D-aspartate receptor NR3A subunit on prepulse inhibition of startleSuzanne 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... - BI-1 regulates an apoptosis pathway linked to endoplasmic reticulum stressHan 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... - Molecular pathways to neurodegenerationElla 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.... - Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activityDongdong 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... - Acute neuroprotective synergy of erythropoietin and insulin-like growth factor IMurat 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... - Erythropoietin protects cerebrocortical neurons from HIV-1/gp120-induced damageMurat 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... - Turning down, but not offStuart A Lipton
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
Nature 428:473. 2004 - Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cellsJinjuan 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... - 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.... - Sporadic ALS: blame it on the editorStuart A Lipton
Nat Med 10:347. 2004
Research Grants
- RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERSStuart 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. ..
- RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERSStuart 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. ..
- Caspase Cleavage of MEF2 Mediates Neuronal ApoptosisStuart Lipton; Fiscal Year: 2007....
- S-Nitrosylation of Matrix Metalloproteinases in AIDSStuart 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. ..
- La Jolla Interdisciplinary Neuroscience Center CoresStuart Lipton; Fiscal Year: 2007....
- Erythropoietin PLUS IGF-IN NEUROPROTECTION FROM AIDSStuart 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. ..
- RETINAL GANGLION CELLS: ION CHANNELS & TRANSMITTERSStuart 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. ..
- AIDS-Related Neurotoxicity and Novel NMDAR AntagonistsStuart 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. ..
- AIDS-RELATED NEUROTOXCITY: GP120 AND CHEMOKINESStuart 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. ..
- Chemokines and Macrophages in HIV Neuronal ApoptosisStuart Lipton; Fiscal Year: 2003..Neuronal apoptosis due to gp120 or chemokines will be monitored using several approaches. ..
- ERYTHROPOIETIN-INDUCED NEUROPROTECTIONStuart Lipton; Fiscal Year: 2005....
- RETINAL GANGLION CELLS--ION CHANNELS & TRANSMITTERSStuart 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. ..