Research Topics
| Jeffrey RothsteinSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Publications
Current hypotheses for the underlying biology of amyotrophic lateral sclerosisJeffrey D Rothstein
Department of Neurology and Neuroscience, Brain Science Institute, Johns Hopkins University, Baltimore, MD 21287, USA
Ann Neurol 65:S3-9. 2009..Convergence of these pathways is likely to mediate disease onset and progression...
Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosisRenee Douville
Department of Neurology, Johns Hopkins University, Baltimore, MD, USA
Ann Neurol 69:141-51. 2011..Previous studies showed reverse transcriptase in serum of ALS patients at levels comparable to human immunodeficiency virus-infected patients; however, the source and significance of the retroviral elements is uncertain...
Ceftriaxone protects against the neurotoxicity of human immunodeficiency virus proteinsJeffrey A Rumbaugh
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Neurovirol 13:168-72. 2007..Ceftriaxone produced dose-dependent attenuation of the neurotoxicity and neuronal cell death caused by both viral proteins. This study demonstrates that this class of drugs may have therapeutic efficacy in HIV dementia...- Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loadingJamuna R Subramaniam
Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA
Nat Neurosci 5:301-7. 2002..Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models... - Biochemical markers: proJeffrey Rothstein
Johns Hopkins University, Baltimore, MD, USA
Amyotroph Lateral Scler Other Motor Neuron Disord 3:S81. 2002 - Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factorsJeronia Llado
Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA
Mol Cell Neurosci 27:322-31. 2004..We also showed that NSCs can protect spinal cord cultures from experimentally induced excitotoxic damage. The neuroprotective potential of NSCs was further confirmed in vivo by their ability to protect against motor neuron cell death... - Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicityJessica Darman
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Neurosci 24:7566-75. 2004..Similar changes may occur in other motor neuron disorders such as amyotrophic lateral sclerosis or West Nile Virus-induced poliomyelitis, suggesting a common tissue injury pathway... - Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNSMelissa R Regan
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA
J Neurosci 27:6607-19. 2007.... - Glial restricted precursors protect against chronic glutamate neurotoxicity of motor neurons in vitroNicholas J Maragakis
Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, Maryland 21287, USA
Glia 50:145-59. 2005..The seeding of G3s resulted in a reduction of motor neuron cell death. Hence, we believe that these cells may potentially play a role in cell-based neuroprotection from glutamate excitotoxicity... - Selective up-regulation of the glial Na+-dependent glutamate transporter GLT1 by a neuroimmunophilin ligand results in neuroprotectionRaquelli Ganel
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
Neurobiol Dis 21:556-67. 2006..These studies suggest that neuroimmunophilins can regulate GLT1 and that their ligands could serve as therapies for neurodegenerative disorders... - Astrocyte glutamate transporters regulate metabotropic glutamate receptor-mediated excitation of hippocampal interneuronsYanhua H Huang
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Neurosci 24:4551-9. 2004.... - Regulation of astrocytic glutamate transporter expression by Akt: evidence for a selective transcriptional effect on the GLT-1/EAAT2 subtypeLi-Bin Li
Department of Pediatrics, University of Pennsylvania, Philadelphia, Pensylvania 19104-4318, USA
J Neurochem 97:759-71. 2006..From these studies, we conclude that Akt induces the expression of GLT-1 through increased transcription and that Akt can regulate GLT-1 expression without increasing GLAST expression in astrocytes... - Loss of the astrocyte glutamate transporter GLT1 modifies disease in SOD1(G93A) miceAndrea C Pardo
Department of Neurology, Johns Hopkins University, 600 N Wolfe St, Meyer 6 119, Baltimore, MD 21287, USA
Exp Neurol 201:120-30. 2006..This study suggests that astrocytes, and the astrocyte glutamate transporter GLT1, play a role in modifying disease progression and motor neuron loss in this model... - Recovery from paralysis in adult rats using embryonic stem cellsDeepa M Deshpande
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287-6965, USA
Ann Neurol 60:32-44. 2006..To our knowledge, this is the first report of the anatomical and functional replacement of a motor neuron circuit within the adult mammalian host... - The glutamate-aspartate transporter GLAST mediates glutamate uptake at inner hair cell afferent synapses in the mammalian cochleaElisabeth Glowatzki
Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Neurosci 26:7659-64. 2006..These data indicate that GLAST in supporting cells is responsible for transmitter uptake at IHC afferent synapses... - Analysis of cerebellar Purkinje cells using EAAT4 glutamate transporter promoter reporter in mice generated via bacterial artificial chromosome-mediated transgenesisDan Gincel
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
Exp Neurol 203:205-12. 2007..The correlation of promoter activity to protein expression makes the EAAT4 BAC promoter reporter a valuable tool to study regulation of EAAT4 expression... - Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor traffickingChen Lai
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892 3707, USA
J Neurosci 26:11798-806. 2006.... - Mechanisms of Disease: astrocytes in neurodegenerative diseaseNicholas J Maragakis
Department of Neurology, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Meyer 6 119, Baltimore, MD 21287, USA
Nat Clin Pract Neurol 2:679-89. 2006..These models have led to the development of targeted therapies for pathways in which astrocytes participate, and this research should ultimately influence the clinical treatment of neurodegenerative disorders... - Targeting an old mechanism in a new disease-protection of glutamatergic dysfunction in depressionRita Sattler
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
Biol Psychiatry 61:137-8. 2007 - Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALSAngelo C Lepore
Department of Neurology, The Johns Hopkins University School of Medicine, 600 N Wolfe St, Meyer 6 109, Baltimore, MD 21287, USA
Brain Res 1185:256-65. 2007.... - Reticulon RTN2B regulates trafficking and function of neuronal glutamate transporter EAAC1Yiting Liu
Departments of Neurology and Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
J Biol Chem 283:6561-71. 2008..These studies indicate that transporter exit from the ER controlled by the interaction with its ER binding partner represents a critical regulatory step in glutamate transporter trafficking to the cell surface... - Motor neuron disease occurring in a mutant dynactin mouse model is characterized by defects in vesicular traffickingFiona M Laird
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Neurosci 28:1997-2005. 2008..This novel mouse model will be instrumental for not only clarifying disease mechanisms in ALS, but also for testing therapeutic strategies to ameliorate this devastating disease... - Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult ratsJames M Harper
Department of Neurology, Johns Hopkins University School of Medicine, Pathology 627C, 600 North Wolfe Street, Baltimore, MD 21287, USA
Proc Natl Acad Sci U S A 101:7123-8. 2004.... - Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expressionJeffrey D Rothstein
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287, USA
Nature 433:73-7. 2005..Thus these studies provide a class of potential neurotherapeutics that act to modulate the expression of glutamate neurotransmitter transporters via gene activation... - Translocation of glutamate transporter subtype excitatory amino acid carrier 1 protein in kainic acid-induced rat epilepsyAkiko Furuta
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Am J Pathol 163:779-87. 2003..Our results suggest that the transient EAAC1 internalization participates in the modulation of the transporter function preventing excessive glutamate uptake to pyramidal neurons during the early stage of epilepsy... - Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injuryDouglas A Kerr
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
J Neurosci 23:5131-40. 2003..We conclude that cells derived from human pluripotent stem cells have the capacity to restore neurologic function in animals with diffuse motor neuron disease via enhancement of host neuron survival and function... - NAALADase inhibition protects motor neurons against chronic glutamate toxicityAjit G Thomas
Guilford Pharmaceuticals Inc, 6611 Tributary Street, Baltimore, MD 21224, USA
Eur J Pharmacol 471:177-84. 2003..Results suggest that NAALADase inhibitors protect against chronic glutamate-mediated motor neuron degeneration and may prove therapeutic towards amyotrophic lateral sclerosis... - Topiramate protects against motor neuron degeneration in organotypic spinal cord cultures but not in G93A SOD1 transgenic miceNicholas J Maragakis
Johns Hopkins University, Department of Neurology, Meyer 6-109, 600 North Wolfe Street, Baltimore, MD 21287, USA
Neurosci Lett 338:107-10. 2003..These studies suggest that topiramate could be useful as a neuroprotectant, but were not effective in more complex motor injury paradigms such as the mouse model of ALS... - Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALSDaniel B Drachman
Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Meyer 6-109, 600 N. Wolfe Street, Baltimore, MD 21287-7519, USA
Ann Neurol 52:771-8. 2002..Spinal cords of treated ALS mice showed significant preservation of spinal neurons and diminished astrogliosis and microglial activation. Our results suggest that cyclooxygenase-2 inhibition may benefit ALS patients... - Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120Zhuying Wang
Molecular Virology Division, St Luke s Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, NY 10019, USA
Virology 312:60-73. 2003..Reduction of the ability of HIV-1-infected astrocytes to take up glutamate may contribute to the development of neurological disease... - Paving new pathwaysJeffrey D Rothstein
Nat Med 8:938-40. 2002 - A neuronal glutamate transporter contributes to neurotransmitter GABA synthesis and epilepsyJehuda P Sepkuty
Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287-7247, USA
J Neurosci 22:6372-9. 2002..EAAC1 may participate in normal GABA neurosynthesis and limbic hyperexcitability, whereas epilepsy can result from a disruption of the interaction between EAAC1 and GABA metabolism... - Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan diseaseJasper E Visser
Department of Neurology, Meyer 6 181, Johns Hopkins Hospital, Baltimore, MD 21287, USA
Brain Res Dev Brain Res 133:127-39. 2002..Overall, these data provide evidence for increased oxidative stress, but the failure to protect the knockout mice by over-expressing SOD1 argues that oxidative stress is not the sole process responsible for the loss of striatal dopamine... - Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS)David S Howland
Department of Molecular Genetics, Wyeth Research, CN8000, Princeton, NJ 08543, USA
Proc Natl Acad Sci U S A 99:1604-9. 2002..These transgenic rats provide a valuable resource to pursue experimentation and therapeutic development, currently difficult or impossible to perform with existing ALS transgenic mice... - Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS modelBrian K Kaspar
Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Science 301:839-42. 2003..We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms... - Glutamate transporters: animal models to neurologic diseaseNicholas J Maragakis
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
Neurobiol Dis 15:461-73. 2004..Recent work has focused on glutamate transporter biology in human diseases with an emphasis on how manipulation of these transporter proteins may lead to therapeutic interventions in neurologic disease... - Reality and immortality--neural stem cells for therapiesJeffrey D Rothstein
Nat Biotechnol 22:283-5. 2004 - Glutamate transporter expression and function in human glial progenitorsNicholas J Maragakis
Department of Neurology and Neuroscience, Johns Hopkins University, Meyer 6-109, 600 N. Wolfe Street, Baltimore, MD 21287-5953, USA
Glia 45:133-43. 2004.... - Glutamate receptor antagonists protect from virus-induced neural degenerationJennifer L Nargi-Aizenman
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA
Ann Neurol 55:541-9. 2004..Furthermore, AMPA receptor-mediated motor neuron death is an important contributor to paralysis and mortality in acute alphavirus-induced encephalomyelitis... - Aquaporin 4 is increased in association with human immunodeficiency virus dementia: implications for disease pathogenesisCoryse St Hillaire
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
J Neurovirol 11:535-43. 2005..Additional studies may be warranted to determine whether altered AQP4 expression represents a protective and/or maladaptive response to central nervous system (CNS) inflammation... - Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosisRoy G Cutler
Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD, USA
Ann Neurol 52:448-57. 2002..These findings suggest a pivotal role for altered sphingolipid metabolism in the pathogenesis of ALS... - Retinal colocalization and in vitro interaction of the glutamate transporter EAAT3 and the serum- and glucocorticoid-inducible kinase SGK1 [correction]Roman Schniepp
Department of Physiology I, , Germany
Invest Ophthalmol Vis Sci 45:1442-9. 2004..This function is shared by protein kinase B (PKB). The experiments reveal a novel mechanism regulating EAAT3, which may be essential for the function of the retinal ganglion cells... - Preclinical studies: how much can we rely on?Jeffrey D Rothstein
Johns Hopkins University, USA
Amyotroph Lateral Scler Other Motor Neuron Disord 5:22-5. 2004 - The endoplasmic reticulum exit of glutamate transporter is regulated by the inducible mammalian Yip6b/GTRAP3-18 proteinALICIA M RUGGIERO
Department of Neuroscience, Johns Hopkins University, 625 N Wolfe Street, Baltimore, MD 21287, USA
J Biol Chem 283:6175-83. 2008..The features of GTRAP3-18 activity are consistent with recent phylogenic sequence analyses suggesting GTRAP3-18 and JM4 be reclassified as mammalian isoforms of the yeast protein family Yip, Yip6b, and Yip6a, respectively... - Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cellsQin Wang
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109, USA
J Biol Chem 279:28831-4. 2004..Suppression of p115rhoGEF had no effect. Thus different rhoGEFs (LARG and PDZrhoGEF) mediate downstream rho signaling by the thrombin and LPA receptors... - Models of amyotrophic lateral sclerosisMandy Jackson
Johns Hopkins University, Baltimore, Maryland, USA
Curr Protoc Neurosci . 2002..Appropriate animal and cell culture models of ALS can be used to help unravel the sequence of events in motor neuronal degeneration and test potential therapies... - TDP-43 in amyotrophic lateral sclerosis: pathophysiology or patho-babel?Jeffrey D Rothstein
Ann Neurol 61:382-4. 2007 - Therapeutic immunization with a glatiramer acetate derivative does not alter survival in G93A and G37R SOD1 mouse models of familial ALSChristine Haenggeli
Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA
Neurobiol Dis 26:146-52. 2007..The biological response in animals, and ultimate clinical translation, will ultimately be dependent on careful and appropriate dose, route and carrier paradigms... - Altered expression of the glutamate transporter EAAT2b in neurological diseaseNicholas J Maragakis
Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Ann Neurol 55:469-77. 2004..These studies clearly document altered regulation and splicing of the dominant glutamate transporter EAAT2 under conditions of neurological stress... - Spectrin mutations cause spinocerebellar ataxia type 5Yoshio Ikeda
Department of Genetics, Cell Biology, and Development, University of Minnesota, 321 Church St SE, Minneapolis, Minnesota 55455 USA
Nat Genet 38:184-90. 2006..Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling... - Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: link between microtubules, actin cytoskeleton, and neuronal polarityDavid M Longhurst
Centre for Neuroscience Research, The University of Edinburgh, Edinburgh EH9 1QH, Scotland, United Kingdom
J Biol Chem 281:12030-40. 2006..This coordinated action of the actin and microtubular cytoskeletons is essential for the development and maintenance of neuronal polarity... - Climbing fiber activation of EAAT4 transporters and kainate receptors in cerebellar Purkinje cellsYanhua H Huang
Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205, USA
J Neurosci 24:103-11. 2004..In GluR5 knock-out mice, this current was dramatically reduced, indicating that CF excitation of PCs involves two distinct classes of ionotropic glutamate receptors, AMPA receptors and GluR5-containing kainate receptors... - Mechanisms for reversible regulation between G13 and Rho exchange factorsClark D Wells
Department of Pharmacology, University of Texas, Southwestern Medical Center at Dallas, Texas 75390-9041, USA
J Biol Chem 277:1174-81. 2002..These results suggest a mechanism for activation of the nucleotide exchange activity of p115 RhoGEF that involves direct and coordinate interaction of Galpha(13) to both its RGS and DH domains... - Degeneration of respiratory motor neurons in the SOD1 G93A transgenic rat model of ALSJeronia Llado
Department of Neurology, Johns Hopkins University 600 N Wolfe Street, Meyer 6 119, Baltimore, MD 21287, USA
Neurobiol Dis 21:110-8. 2006..Taken together, these data suggest that respiratory motor neuron loss results in significant electrophysiologic changes and diaphragmatic atrophy. These changes may play a significant role resulting in death of these animals... - Signal-crosstalk between Rho/ROCK and c-Jun NH2-terminal kinase mediates migration of vascular smooth muscle cells stimulated by angiotensin IIHaruhiko Ohtsu
Cardiovascular Research Center, Temple University School of Medicine, 3420 N Broad St, Philadelphia, PA 19140, USA
Arterioscler Thromb Vasc Biol 25:1831-6. 2005.... - Expression of glutamate transporter subtypes during normal human corticogenesis and type II lissencephalyAkiko Furuta
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1, Ogawahigashi, Kodaira, Tokyo 187 8502, Japan
Brain Res Dev Brain Res 155:155-64. 2005..Altered glutamate transporter expression in type II lissencephaly suggests that glutamate metabolism is involved in the formation of the normal cortex and contributes to the disorganized cortex seen in migration disorders... - Of mice and men: reconciling preclinical ALS mouse studies and human clinical trialsJeffrey D Rothstein
Ann Neurol 53:423-6. 2003 - Glucocorticoid regulation of GLT-1 glutamate transporter isoform expression in the rat hippocampusAnita E Autry
Department of Pharmacology, Physiology and Neuroscience, School of Medicine, University of South Carolina, Columbia, SC 29208, USA
Neuroendocrinology 83:371-9. 2006..These studies suggest that GLT-1b expression is regulated by stress levels of glucocorticoids (GCs) and GLT-1 expression is regulated by stress-induced increases in extracellular glutamate levels in the CA3 region...
Research Grants
- Astroglial Monocarboxylate Transporter (MCT) Pathway in NeurodegenerationJeffrey D Rothstein; Fiscal Year: 2010....
- Characterizing Beta Lactams/Neuroprotective Drugs/ALSJeffrey Rothstein; Fiscal Year: 2006..These sequential phases will set the stage for future practical translation towards rational clinical trial design. ..
- Stem Cell Therapy for Motor Neuron DiseaseJeffrey Rothstein; Fiscal Year: 2006..abstract_text> ..
- MECHANISMS FOR ABERRANT GLUTAMATE TRANSPORT IN ALSJeffrey Rothstein; Fiscal Year: 2003..Aberrant RNA processing could bed an important process in the pathophysiology of neurodegenerative disease and in excitotoxicity. The presence of these mRNA species in also cerebrospinal fluid may have diagnostic utility. ..
- Astroglial Monocarboxylate Transporter (MCT) Pathway in NeurodegenerationJeffrey D Rothstein; Fiscal Year: 2010....
- Therapeutic Expression of Glial Glutamate TransportersJeffrey Rothstein; Fiscal Year: 2009....
- Neuronal vs. glial glutamate transport regulation in ALSJeffrey Rothstein; Fiscal Year: 2009..These studies will help determine if the altered expression of GLT1b in disease is an important physiological response. They will also provide basic physiological properties of the neuronal versus glial pools of GLT1 and GLT1b. ..
- Therapeutic Expression of Glial Glutamate TransportersJeffrey Rothstein; Fiscal Year: 2007....
- Stem Cell Therapy for Motor Neuron DiseaseJeffrey Rothstein; Fiscal Year: 2007..abstract_text> ..
- NEURONAL GLUTAMATE TRANSPORTER ASSOCIATED PROTEINS(GTRAPJeffrey Rothstein; Fiscal Year: 2004..3) Evaluate the cellular and ultrastructural distribution of GTRAPs and 4) to determine the physiological regulation of neuronal glutamate transporters by these novel GTRAPs. ..
- Stem Cell Therapy for Motor Neuron DiseaseJeffrey Rothstein; Fiscal Year: 2003..abstract_text> ..
- COPPER CHAPERONE FOR SOD1 (CCS) AND MOTOR NEURON DISEASEJeffrey Rothstein; Fiscal Year: 2002..Overall, these experiments will help test the hypothesis that 1) CCS is responsible for the cytoplasmic aggregates in astrocytes and neurons, and 2) that CCS participates in mutant SOD1 mediated neurotoxicity. ..