Research Topics
| Rajiv RatanSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Antioxidants, HIF prolyl hydroxylase inhibitors or short interfering RNAs to BNIP3 or PUMA, can prevent prodeath effects of the transcriptional activator, HIF-1alpha, in a mouse hippocampal neuronal lineLeila R Aminova
Department of Neurology, Harvard Medical School and BIDMC, Boston, Massachusetts, USA
Antioxid Redox Signal 10:1989-98. 2008..The findings offer strategies for minimizing the prodeath effects of HIF-1 in neurologic conditions associated with hypoxia and oxidative stress, such as stroke and spinal cord injury...
Translation of ischemic preconditioning to the patient: prolyl hydroxylase inhibition and hypoxia inducible factor-1 as novel targets for stroke therapyRajiv R Ratan
Department of Neurology and Neuroscience, Burke Cornell Medical Research Institute, Weill Medical College of Cornell, White Plains, NY 10605, USA
Stroke 35:2687-9. 2004..Here, we review evidence suggesting that the HIF-1 prolyl hyroxylases are inhibited during ischemic preconditioning and that pharmacological inhibitors of these enzymes are viable targets for stroke therapy...- Mining genome databases for therapeutic gold: SIM2 is a novel target for treatment of solid tumorsRajiv R Ratan
Department of Neurology, Program in Neuroscience, and Center for Neurodegeneration and Repair, Harvard Medical School and Burke/Cornell Medical Research Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
Trends Pharmacol Sci 24:508-10. 2003 - Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotectionBrett Langley
Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 28:163-76. 2008.... - A large-scale chemical screen for regulators of the arginase 1 promoter identifies the soy isoflavone daidzeinas a clinically approved small molecule that can promote neuronal protection or regeneration via a cAMP-independent pathwayThong C Ma
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 30:739-48. 2010.... - HIF prolyl hydroxylase inhibitors prevent neuronal death induced by mitochondrial toxins: therapeutic implications for Huntington's disease and Alzheimer's diseaseZoya Niatsetskaya
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
Antioxid Redox Signal 12:435-43. 2010.... - CD36 is involved in astrocyte activation and astroglial scar formationYi Bao
Burke Cornell Medical Research Institute, White Plains, New York, USA
J Cereb Blood Flow Metab 32:1567-77. 2012..These findings identify CD36 as a novel mediator for injury-induced astrogliosis and scar formation. Targeting CD36 may serve as a potential strategy to reduce glial scar formation in stroke... - Prolyl 4-hydroxylase activity-responsive transcription factors: from hydroxylation to gene expression and neuroprotectionAmbreena Siddiq
Burke Medical Research Institute, White Plains, New York 10605, USA
Front Biosci 13:2875-87. 2008.... - Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous systemAmbreena Siddiq
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:41732-43. 2005..Taken together these findings identified low molecular weight and peptide HIF prolyl 4-hydroxylase inhibitors as novel neurological therapeutics for stroke as well as other diseases associated with oxidative stress... - Prosurvival and prodeath effects of hypoxia-inducible factor-1alpha stabilization in a murine hippocampal cell lineLeila R Aminova
Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 280:3996-4003. 2005..Together, these data demonstrate that HIF-1 can mediate prodeath or prosurvival responses in the same cell type depending on the injury stimulus... - Proteasome inhibition protects HT22 neuronal cells from oxidative glutamate toxicityKlaus van Leyen
Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
J Neurochem 92:824-30. 2005..These findings suggest that caspases can be decoupled from oxidative stress under some conditions, and implicate the ubiquitin/proteasome pathway in neuronal cell death caused by oxidative glutamate toxicity... - Remodeling chromatin and stress resistance in the central nervous system: histone deacetylase inhibitors as novel and broadly effective neuroprotective agentsBrett Langley
Burke Medical Research Institute, White Plains, NY 10605, USA
Curr Drug Targets CNS Neurol Disord 4:41-50. 2005..These studies demonstrate that pharmacological HDAC inhibition is a promising therapeutic approach for the treatment of a range of central nervous system disorders... - Novel roles for arginase in cell survival, regeneration, and translation in the central nervous systemPhilipp S Lange
Department of Neurology, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston MA 02115, USA
J Nutr 134:2812S-2817S; discussion 2818S-2819S. 2004..Beyond molecular mechanisms, this review will also include relevant clinical findings in patients with neurodegenerative diseases... - Oxidative stress-induced death in the nervous system: cell cycle dependent or independent?Brett Langley
Department of Neurology, Harvard Medical School and the Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
J Neurosci Res 77:621-9. 2004..The determining factor for which or how many pathways are induced appears to be context dependent and determined by the level and duration of oxidative stress... - The role of iron neurotoxicity in ischemic strokeMagdy H Selim
Department of Neurology, Division of Cerebrovascular Diseases, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Palmer 127, Boston, MA 02215, USA
Ageing Res Rev 3:345-53. 2004..Understanding the changes in brain iron metabolism and its relationship to neuronal injury in ischemic stroke could provide new therapeutic targets to improve the outcome of stroke patients... - Sp1 and Sp3 are oxidative stress-inducible, antideath transcription factors in cortical neuronsHoon Ryu
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 23:3597-606. 2003..Taken together, these results establish Sp1 and Sp3 as oxidative stress-induced transcription factors in cortical neurons that positively regulate neuronal survival... - Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathwayHoon Ryu
Department of Neurology and Program in Neuroscience, Harvard Medical School and Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4281-6. 2003..Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response... - Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion modelJuergen Bardutzky
Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA
J Cereb Blood Flow Metab 25:968-77. 2005..This effect was mainly observed in the cortex. Our data suggest that DMSO represents an interesting candidate for acute stroke treatment... 
Harnessing hypoxic adaptation to prevent, treat, and repair strokeRajiv R Ratan
Winifred Masterson Burke Medical Research Institute, White Plains, NY 10605, USA
J Mol Med (Berl) 85:1331-8. 2007..The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics...- ATF4 is an oxidative stress-inducible, prodeath transcription factor in neurons in vitro and in vivoPhilipp S Lange
Burke Medical Research Institute, White Plains, NY 10605, USA
J Exp Med 205:1227-42. 2008..Collectively, these findings establish ATF4 as a redox-regulated, prodeath transcriptional activator in the nervous system that propagates death responses to oxidative stress in vitro and to stroke in vivo... - Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathwaysAmbreena Siddiq
Department of Neurosciences, Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 29:8828-38. 2009.... - Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stressAmbreena Siddiq
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Neurochem Res 32:931-46. 2007.... - HDAC6 is a target for protection and regeneration following injury in the nervous systemMark A Rivieccio
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Proc Natl Acad Sci U S A 106:19599-604. 2009..Together, these findings define HDAC6 as a potential nontoxic therapeutic target for ameliorating CNS injury characterized by oxidative stress-induced neurodegeneration and insufficient axonal regeneration... - In vitro model of oxidative stress in cortical neuronsRajiv R Ratan
Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA
Methods Enzymol 352:183-90. 2002 
Utilization of an in vivo reporter for high throughput identification of branched small molecule regulators of hypoxic adaptationNatalya A Smirnova
Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Chem Biol 17:380-91. 2010....- Arginase 1 regulation of nitric oxide production is key to survival of trophic factor-deprived motor neuronsALVARO G ESTEVEZ
Burke Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 26:8512-6. 2006..They also suggest that the resistance of motor neuron subpopulations to trophic factor deprivation may result from increased arginase activity... - Controlled enzymatic production of astrocytic hydrogen peroxide protects neurons from oxidative stress via an Nrf2-independent pathwayRENEE E HASKEW-LAYTON
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, The Burke Medical Research Institute, White Plains, NY 10605, USA
Proc Natl Acad Sci U S A 107:17385-90. 2010..These findings demonstrate the utility of rgDAAO for spatially and temporally controlling intracellular H(2)O(2) concentrations to uncover unique astrocyte-dependent neuroprotective mechanisms... - The histone deacetylase inhibitor sodium butyrate protects against cisplatin-induced hearing loss in guinea pigsMarie Drottar
Department of Otolaryngology, Children's Hospital, and the Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, USA
Laryngoscope 116:292-6. 2006..Because histone deacetylase inhibitors are anticancer agents with very few side effects, they may be candidates for clinical use during cisplatin chemotherapy... - Transcriptional therapy with the histone deacetylase inhibitor trichostatin A ameliorates experimental autoimmune encephalomyelitisSandra Camelo
Laboratory of Transcriptional and Immune Regulation, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02139, USA
J Neuroimmunol 164:10-21. 2005..A transcriptional imbalance in MS may contribute to immune dysregulation and neurodegeneration, and we identify HDAC inhibition as a transcriptional intervention to ameliorate this imbalance... - Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survivalJunghee Lee
Neurology Department, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 280:40398-401. 2005.... - Genetic variant of BDNF (Val66Met) polymorphism attenuates stroke-induced angiogenic responses by enhancing anti-angiogenic mediator CD36 expressionLuye Qin
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
J Neurosci 31:775-83. 2011..The results suggest that CD36 inhibition may be a viable strategy to enhance angiogenesis and possible recovery in human stroke victims who are Met homozygotes at codon 66 of the BDNF locus... - New perspectives on developing acute stroke therapyMarc Fisher
Department of Neurology, University of Massachusetts Medical School, Worcester 01605, USA
Ann Neurol 53:10-20. 2003..Combining knowledge from these three areas provides optimism that additional acute stroke therapies can be developed to maximize beneficial functional outcome in the greatest proportion of acute stroke patients possible... - Cause and consequence: mitochondrial dysfunction initiates and propagates neuronal dysfunction, neuronal death and behavioral abnormalities in age-associated neurodegenerative diseasesGary E Gibson
Department of Neurology and Neuroscience, Weill Cornell Medical College of Cornell University at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Biochim Biophys Acta 1802:122-34. 2010..Altogether, our results suggest that increasing KGDHC via inhibition of TGase or via a host of other strategies to be described would be effective therapeutic approaches in age-associated neurodegenerative diseases... - Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's diseaseGabriella Gardian
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, New York 10021, USA
J Biol Chem 280:556-63. 2005.... - The metabolic coupling of arginine metabolism to nitric oxide generation by astrocytesJoann M Gensert
Burke Cornell Medical Research Institute, White Plains, New York 10605, USA
Antioxid Redox Signal 8:919-28. 2006..Thus, neural and nonneural cells act in concert to affect neuron physiology in an elegantly integrated system. This review focuses on the components of the interaction between astrocytes and neurons in nitric oxide biology... - CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cellsJoann M Gensert
The Winifred Masterson Burke Cornell Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Neurobiol Dis 26:671-80. 2007..Induction of CD81 expression through HDAC inhibition is a novel strategy to promote growth arrest in glioma cells... - Histone deacetylase inhibitors de-repress tyrosine hydroxylase expression in the olfactory bulb and rostral migratory streamYosuke Akiba
Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA
Biochem Biophys Res Commun 393:673-7. 2010.... - Novel multi-modal strategies to promote brain and spinal cord injury recoveryRajiv R Ratan
Winifred Masterson Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Stroke 40:S130-2. 2009..We conclude that combinations of interventions will be needed to surmount the multiple barriers to recovery in stroke and other types of brain and spinal cord injury recovery... - Translational control of inducible nitric oxide synthase expression by arginine can explain the arginine paradoxJunghee Lee
Deparment of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 100:4843-8. 2003..These results provide an explanation for the arginine paradox for iNOS and define a distinct mechanism by which a substrate can regulate the activity of its associated enzyme... - The c-Raf inhibitor GW5074 provides neuroprotection in vitro and in an animal model of neurodegeneration through a MEK-ERK and Akt-independent mechanismPaul C Chin
Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083, USA
J Neurochem 90:595-608. 2004.... - Molecular basis of vitamin E action: tocotrienol modulates 12-lipoxygenase, a key mediator of glutamate-induced neurodegenerationSavita Khanna
Laboratory of Molecular Medicine, Department of Surgery, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio 43210, USA
J Biol Chem 278:43508-15. 2003..These findings lend further support to alpha-tocotrienol as a potent neuroprotective form of vitamin E... - Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage responseJunghee Lee
Geriatric Research Education and Clinical Center, Bedford Veteran s Affairs Medical Center, 200 Springs Rd, Bedford, MA 01730, USA
FASEB J 20:2375-7. 2006..These results indicate that in primary neurons Sp1 and Sp3 play an essential role in the modulation of COX-2 transcription, which mediates neuronal homeostasis and survival by preventing DNA damage in response to neuronal stress... - Arginase I and polyamines act downstream from cyclic AMP in overcoming inhibition of axonal growth MAG and myelin in vitroDongming Cai
Biology Department, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10024, USA
Neuron 35:711-9. 2002..Over-expressing Arginase I in maturing DRGs blocks that switch. Arginase I and polyamines are more specific targets than cAMP for intervention to encourage regeneration after CNS injury... - Therapeutic effects of cystamine in a murine model of Huntington's diseaseAlpaslan Dedeoglu
Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, USA
J Neurosci 22:8942-50. 2002..These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients... - Novel changes in gene expression following axotomy of a sympathetic ganglion: a microarray analysisKristen L Boeshore
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA
J Neurobiol 59:216-35. 2004..In addition, the data suggest a potential role for putrescine and spermidine, acting downstream of arg I, in the regenerative process... - cAMP response element binding protein family transcription factors: the Holy Grail of neurological therapeutics?Rajiv R Ratan
Ann Neurol 56:607-8. 2004 - Oxygen-sensitive reset of hypoxia-inducible factor transactivation response: prolyl hydroxylases tune the biological normoxic set pointSavita Khanna
Laboratory of Molecular Medicine, Davis Heart and Lung Research Institute, Department of Surgery, The Ohio State University Medical Center, Columbus, 43210, USA
Free Radic Biol Med 40:2147-54. 2006..siRNA dependent knockdown of PHD expression revealed that O(2)-sensitive regulation of PHD may contribute to tuning the normoxic set point in biological cells... - Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's diseaseRobert J Ferrante
Geriatric Research and Education and Clinical Center, Veterans Administration Medical Center, Bedford, MA, USA
J Neurosci 24:10335-42. 2004..Because it is Food and Drug Administration-approved, mithramycin is a promising drug for the treatment of HD... - Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neuronsHoon Ryu
Geriatric Research Education and Clinical Center, Veteran s Affairs Medical Center, Bedford, MA 01730, USA
Proc Natl Acad Sci U S A 102:13915-20. 2005..These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons...
Research Grants
- NEUROPROTECTIVE GENE INDUCTION BY ANTIOXIDANT IRON CHELARajiv Ratan; Fiscal Year: 2002..Furthermore, these studies also promise to further define mechanisms of protection by small molecule iron chelators. ..
- Arginase and Regulation of Nitric Oxide Synthase in ALSRajiv Ratan; Fiscal Year: 2004..These studies promise to enhance our understanding of how arginine about metabolism, including the synthesis of NO, is regulated in the normal and abnormal nervous system. ..