Research Topics
Genomes and Genes
| Ole IsacsonSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Neuroinflammation mediated by IL-1beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's diseaseJames B Koprich
Center for Neuroregeneration Research, Harvard Medical School McLean Hospital, Belmont, MA 02478, USA
J Neuroinflammation 5:8. 2008..It is more likely that multiple factors converge to give rise to PD than any single cause. Here we report that inflammation can trigger degeneration of dopamine (DA) neurons in an animal model of Parkinson's disease...- Problems and solutions for circuits and synapses in Parkinson's diseaseOle Isacson
Department of Neurology, NINDS Udall Parkinson's Disease Research Center of Excellence, Harvard University Medical School, Belmont, MA 02478, USA
Neuron 43:165-8. 2004 - The production and use of cells as therapeutic agents in neurodegenerative diseasesOle Isacson
Department of Neurology and the Harvard Center for Neurodegeneration and Repair, Harvard Medical School, Boston, MA, USA
Lancet Neurol 2:417-24. 2003.... - Embryonic stem cell-derived Pitx3-enhanced green fluorescent protein midbrain dopamine neurons survive enrichment by fluorescence-activated cell sorting and function in an animal model of Parkinson's diseaseEva Hedlund
Udall Parkinson s Disease Research Center for Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
Stem Cells 26:1526-36. 2008..Disclosure of potential conflicts of interest is found at the end of this article... - Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantationS Chung
Udall Parkinson's Disease Research Center of Excellence, McLean Hospital, Belmont, MA 02178, USA
J Neurochem 97:1467-80. 2006..Taken together, our results demonstrate that genetic purification of neural precursor cells using FACS isolation can effectively remove unwanted proliferating cell types and avoid tumor formation after transplantation... - Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graftDaniela Ferrari
McLean Hospital/Harvard University Udall Parkinson's Disease Research Center of Excellence, 115 Mill St, Belmont, MA 02478, USA
Eur J Neurosci 24:1885-96. 2006..Despite the heterogeneity of ES-derived graft cell composition, these results demonstrate normal phenotypic specification, conserved natural axonal target selectivity and functionality of DA neurons derived from primate ES cells... - Fate mapping and lineage analyses demonstrate the production of a large number of striatal neuroblasts after transforming growth factor alpha and noggin striatal infusions into the dopamine-depleted striatumAntoine de Chevigny
Udall Parkinson Disease Research Center of Excellence, Center for Neuroregeneration Research, McLean Hospital Harvard Medical School, Belmont, Massachusetts, USA
Stem Cells 26:2349-60. 2008..This work demonstrates that a large population of multipotent striatal C-like cells can be generated in the DA-depleted striatum that do not spontaneously differentiate into DA neurons... - PSD-95 uncouples dopamine-glutamate interaction in the D1/PSD-95/NMDA receptor complexJingping Zhang
New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA
J Neurosci 29:2948-60. 2009..Thus, in addition to its role in receptor stabilization and synaptic plasticity, PSD-95 acts as a brake on the D(1)-NMDA receptor complex and dampens the interaction between them... - Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cellsDong-Wook Kim
Udall Parkinson's Disease Research Center of Excellence, McLean Hospital/Harvard Medical School, Belmont, Massachusetts 02178, USA
Stem Cells 24:557-67. 2006.... - Selection of embryonic stem cell-derived enhanced green fluorescent protein-positive dopamine neurons using the tyrosine hydroxylase promoter is confounded by reporter gene expression in immature cell populationsEva Hedlund
Udall Parkinson s Disease Research Center for Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
Stem Cells 25:1126-35. 2007..Disclosure of potential conflicts of interest is found at the end of this article... - Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's diseaseRosario Sanchez-Pernaute
McLean Hospital Harvard University Udall Parkinson s Disease Research Center of Excellence, McLean Hospital, Belmont, MA 02478, USA
Brain 131:2127-39. 2008..These data provide proof for the concept that parthenogenetic stem cells are a suitable source of functional neurons for therapeutic applications... - Functional enhancement and protection of dopaminergic terminals by RAB3B overexpressionChee Yeun Chung
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 106:22474-9. 2009..These results suggest that RAB3B improves dopamine handling and storage capacity at presynaptic terminals, and confers protection to vulnerable DA neurons... - The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neuronsS Chung
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, Belmont, MA 02178, USA
Mol Cell Neurosci 28:241-52. 2005..These findings may be important for modifying ES cells to generate an optimal cell source for transplantation therapy of PD... - Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific mannerKwang Soo Kim
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
J Neurochem 85:622-34. 2003..Our results suggest that Nurr1 may play a direct role for specification of DA neurotransmitter identity by activating TH gene transcription in a cell context-dependent manner... - Context-dependent neuronal differentiation and germ layer induction of Smad4-/- and Cripto-/- embryonic stem cellsKai Christian Sonntag
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Mol Cell Neurosci 28:417-29. 2005..This demonstrates that Smad4-/- and Cripto-/- ES cells favor a neural fate in vitro, but also express the mesodermal phenotype, implying that deletion of either Smad4 or Cripto is not sufficient to block nonneuronal tissue formation... - Neural precursors derived from human embryonic stem cells maintain long-term proliferation without losing the potential to differentiate into all three neural lineages, including dopaminergic neuronsSunghoi Hong
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
J Neurochem 104:316-24. 2008..These results demonstrate that hES-NP cells have the ability to provide an expandable and unlimited human cell source that can develop into specific neuronal and glial subtypes... - Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathwaySangmi Chung
Department of Psychiatry and Program in Neuroscience, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Cell Stem Cell 5:646-58. 2009..Together with previous works, this study shows that two regulatory loops (Wnt1-Lmx1a and SHH-FoxA2) critically link extrinsic signals to cell-intrinsic factors and cooperatively regulate mDA neuron development... - Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (cyno-1) after transplantationRosario Sanchez-Pernaute
McLean Hospital Harvard University Udall Parkinson s Disease Research Center of Excellence and Neuroregeneration Laboratories, McLean Hospital, 115 Mill St, Belmont, Massachusetts 02478, USA
Stem Cells 23:914-22. 2005..Optimization of differentiation, cell selection, and cell transfer is required for functional studies of ES-derived DA neurons for future therapeutic applications... - Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by Netrin-1 and SlitsLing Lin
Udall Parkinson s Disease Research Center of Excellence and Neuroregeneration Laboratories, Harvard Medical School McLean Hospital, Belmont, Massachusetts 02478, USA
Stem Cells 24:2504-13. 2006..This may result from developmental differences generated by present in vitro methods of cell patterning or conditioning during ES cell differentiation... - Functional analysis of various promoters in lentiviral vectors at different stages of in vitro differentiation of mouse embryonic stem cellsSunghoi Hong
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
Mol Ther 15:1630-9. 2007..Our results demonstrate that different cellular and viral promoters exhibit very distinct and dynamic properties not only in terms of promoter strength but also with respect to differentiation stage-specific activity... - Proteasome inhibition causes nigral degeneration with inclusion bodies in ratsKevin St P McNaught
Department of Neurology, Mount Sinai School of Medicine, Annenberg 14 73, One Gustave L Levy Place, New York, NY 10029, USA
Neuroreport 13:1437-41. 2002..These findings support the notion that failure of the ubiquitin-proteasome system to degrade and clear unwanted proteins is an important etiopathogenic factor in Parkinson's disease... - Stem cells may reshape the prospect of Parkinson's disease therapyKai Christian Sonntag
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
Brain Res Mol Brain Res 134:34-51. 2005..Here, we summarize the current state of ES cell-derived DA neurogenesis and discuss the aspects involved in generating an optimal cell source for cell replacement in PD... - Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitroSangmi Chung
Udall Parkinson's Disease Research Center of Excellence, McLean Hospital/Harvard Medical School, Belmont, Massachusetts 02178, USA
Stem Cells 24:1583-93. 2006..We conclude that ES NPs maintain their developmental potential during in vitro expansion, whereas mouse E12.5 VM NPs do not... - Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neuronsSangmi Chung
Udall Parkinson's Disease Research Center of Excellence, Neuroregeneration Laboratory, McLean Hospital/Harvard Medical School, Belmont, MA 02478, USA
Eur J Neurosci 16:1829-38. 2002.... - Future of cell and gene therapies for Parkinson's diseaseOle Isacson
Department of Neurology Neuroscience, Center for Neuroregeneration Research and National Institute of Neurological Disorders and Stroke Udall Parkinson s Disease Research Center of Excellence, Harvard Medical School McLean Hospital, Belmont, MA, USA
Ann Neurol 64:S122-38. 2008..Future gene and cell therapies are likely to coexist with classic pharmacological therapies because their use can be tailored to individual patients' underlying disease process and need for neuroprotective or restorative interventions... - Mapping dopamine function in primates using pharmacologic magnetic resonance imagingBruce G Jenkins
Massachusetts General Hospital (MGH) Nuclear Magnetic Resonance Center, Athinoula A. Martinos Center for Biomedical Imaging, Boston, Massachusetts 02129, USA
J Neurosci 24:9553-60. 2004..These data indicate that phMRI is a powerful tool for assessment of dynamic changes associated with normal and dysfunctional DA brain circuitry in primates... - The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neuronsChee Yeun Chung
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Brain 133:2022-31. 2010..These results show that orthodenticle homeobox 2 is important for establishing subgroup phenotypes of post-mitotic midbrain dopaminergic neurons and may alter neuronal vulnerability... - Immature and neurally differentiated mouse embryonic stem cells do not express a functional Fas/Fas ligand systemGabriella Brunlid
Harvard Medical School, Center for Neuroregeneration Research, Udall Parkinson s Disease Center of Excellence, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA
Stem Cells 25:2551-8. 2007..Our results indicate that immature and differentiated mouse ES cells do not express a functional Fas/FasL system. Disclosure of potential conflicts of interest is found at the end of this article... - Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathyChee Yeun Chung
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA
J Neurosci 29:3365-73. 2009..These findings can provide ideas for antecedent biomarkers and presymptomatic interventions in PD... - The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex similar to Alzheimer's disease and Down's syndromeHyemyung Seo
Neuroregeneration Laboratories, Center for Neuroregeneration Research, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
J Neurochem 114:1819-26. 2010..Taken together, these results suggest that both the adaptive reactions in the proteostatic network and pathological changes in AD and DS need to be considered in the future potential therapeutics... - Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease modelsHaruhisa Inoue
Neuroregeneration Laboratories, Udall Parkinson s Disease Center of Excellence, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 104:14430-5. 2007.... - Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist nogginKai Christian Sonntag
Center for Neuroregeneration Research, Udall Parkinson s Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
Stem Cells 25:411-8. 2007..After transplantation of differentiated hESCs to a rodent model of PD, some grafts contained human midbrain-like DA neurons. This protocol demonstrates hESC derivation and survival of human DA neurons appropriate for cell therapy in PD... - Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model miceHyemyung Seo
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Exp Neurol 193:469-80. 2005.... - Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protectionChee Yeun Chung
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Hum Mol Genet 14:1709-25. 2005..These results indicate that certain differentially expressed molecules in A9 and A10 DA neurons may play key roles in their relative vulnerability to toxins and PD... - Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiationKai Christian Sonntag
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
Eur J Neurosci 19:1141-52. 2004..This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain-like DA biochemical and functional cellular phenotype independent of neurogenesis... - Development of histocompatible primate-induced pluripotent stem cells for neural transplantationMichela Deleidi
Center for Neuroregeneration Research, Harvard Medical School McLean Hospital, Belmont, Massachusetts 02478, USA
Stem Cells 29:1052-63. 2011.... - Markers and methods for cell sorting of human embryonic stem cell-derived neural cell populationsJan Pruszak
Center for Neuroregeneration Research, McLean Hospital Harvard Medical School, Belmont, Massachusetts 02478, USA
Stem Cells 25:2257-68. 2007.... - Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neuronsLing Lin
Neuroregeneration Laboratories, Mailman Research Center, Harvard Medical School McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Mol Cell Neurosci 28:547-55. 2005..In this system, netrin-1 stimulated and slit-2 opposed DA neurite growth. Such regulation may be important for DA axonal maintenance, regeneration, and phenotypic target recognition... - Global gene expression profiling of somatic motor neuron populations with different vulnerability identify molecules and pathways of degeneration and protectionEva Hedlund
Center for Neuroregeneration Research, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Brain 133:2313-30. 2010..001, ANOVA), indicating that our approach can identify factors that protect or make neurons more susceptible to degeneration... - Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian ratsGunnar Hargus
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 107:15921-6. 2010.... - The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates--evidence from in vivo neuroimaging studiesArnar Astradsson
Harvard University and McLean Hospital, NINDS Udall Parkinson s Disease Research Center of Excellence, Belmont, MA 02478, USA
Neurobiol Dis 35:348-51. 2009.... - Molecular and cellular determinants for generating ES-cell derived dopamine neurons for cell therapyJan Pruszak
Neuroregeneration Laboratories, Center for Neuroregeneration Research, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Adv Exp Med Biol 651:112-23. 2009..This conceptual synopsis outlines current objectives, progress, but also challenges, in deriving midbrain DA neurons from pluripotent stem cells for clinical and scientific applications... - Differentiation of human ES and Parkinson's disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acidOliver Cooper
Neuroregeneration Laboratories, Harvard Medical School McLean Hospital, NINDS Udall Parkinson s Disease Research Center of Excellence, 115 Mill Street, Belmont, MA 02478, USA
Mol Cell Neurosci 45:258-66. 2010.... - CD15, CD24, and CD29 define a surface biomarker code for neural lineage differentiation of stem cellsJan Pruszak
McLean Hospital Harvard Medical School, Center for Neuroregeneration Research, Belmont, Massachusetts 02478, USA
Stem Cells 27:2928-40. 2009..We believe this set of biomarkers enables analysis and selection of neural cell types for developmental studies and pharmacological and therapeutic applications... - Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patientsOliver Cooper
Center for Neuroregeneration Research, NINDS Udall Parkinson s Disease Research Center of Excellence, McLean Hospital, Harvard Medical School, Harvard University, MRC 130, 115 Mill Street, Belmont, MA 02478, USA
J Neurol 256:310-6. 2009.... - Inhibition of the dopamine D1 receptor signaling by PSD-95Jingping Zhang
Department of Psychiatry, Harvard Medical School, New England Primate Research Center, Southborough, Massachusetts 01772, USA
J Biol Chem 282:15778-89. 2007..These studies demonstrate a role for a glutamatergic scaffold in dopamine receptor signaling and trafficking and identify a new potential target for the modulation of abnormal dopaminergic function... - Insights into Parkinson's disease models and neurotoxicity using non-invasive imagingRosario Sanchez-Pernaute
McLean Hospital Harvard University, Udall Parkinson s Disease Research Center of Excellence, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Toxicol Appl Pharmacol 207:251-6. 2005..Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders... - Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patientsHyemyung Seo
Neuroregeneration Laboratories, Center for Neuroregeneration Research, McLean Hospital, Harvard MedicalSchool, 115 Mill Street, Belmont, MA 02478, USA
Hum Mol Genet 17:3144-53. 2008..Changes in HD patients for UPS function, BDNF expression and MCII/III activity are only partially modeled in R6/2 and YAC72 mice, with the latter at 16 months of age being most congruent with the human disease... - The Toll-like receptor-3 agonist polyinosinic:polycytidylic acid triggers nigrostriatal dopaminergic degenerationMichela Deleidi
Center for Neuroregeneration Research, Harvard Medical School McLean Hospital, Belmont, Massachusetts, 02478, USA
J Neurosci 30:16091-101. 2010..New powerful neuroprotective therapies for PD might be considered by targeting critical inflammatory mechanisms, including cytokine-induced neurotoxicity... - Intrastriatal transforming growth factor alpha delivery to a model of Parkinson's disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neuronsOliver Cooper
Harvard University and McLean Hospital, National Institute of Neurological Disorders and Stroke Udall Parkinson's Disease Research Center of Excellence, Belmont, Massachusetts 02478, USA
J Neurosci 24:8924-31. 2004..In summary, the cells in the TGFalpha-induced migratory cellular wave remain undifferentiated and do not differentiate into midbrain-like DA neurons... - In vivo evidence of D3 dopamine receptor sensitization in parkinsonian primates and rodents with l-DOPA-induced dyskinesiasRosario Sanchez-Pernaute
McLean Hospital Harvard University Udall Parkinson s Disease Research Center of Excellence, McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
Neurobiol Dis 27:220-7. 2007.... - A direct role of the homeodomain proteins Phox2a/2b in noradrenaline neurotransmitter identity determinationHyemyung Seo
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
J Neurochem 80:905-16. 2002..Taken together, these findings establish that Phox2a and 2b control the development of NA neurons in part by directly transactivating DBH transcription through interactions with four binding sites clustered in the proximal promoter... - Analysis of different promoter systems for efficient transgene expression in mouse embryonic stem cell linesSangmi Chung
Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA
Stem Cells 20:139-45. 2002..Our data show that individual promoters have different abilities to express reporter gene expression in the ES and other cell types tested... - Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeuticsLing Lin
Neuroregeneration Laboratories, Mailman Research Center, Harvard Medical School and McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Trends Neurosci 32:142-9. 2009..Novel drugs and treatments could emerge from this new understanding... - Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cellsOle Isacson
Udall Parkinson s Disease Research Center of Excellence, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Ann Neurol 53:S135-46; discussion S146-8. 2003..Ultimately, understanding the cell biological principles necessary for generating functional DA neurons can provide many new avenues for better treatment of patients with PD... - Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat modelLars M Bjorklund
Udall Parkinson's Disease Research Center of Excellence, Neuroregeneration Laboratories, and Molecular Neurobiology Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
Proc Natl Acad Sci U S A 99:2344-9. 2002..These results demonstrate that transplanted ES cells can develop spontaneously into DA neurons. Such DA neurons can restore cerebral function and behavior in an animal model of Parkinson's disease... - An endogenous serine/threonine protein phosphatase inhibitor, G-substrate, reduces vulnerability in models of Parkinson's diseaseChee Yeun Chung
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA
J Neurosci 27:8314-23. 2007.... - Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease modelAnna Liisa Brownell
Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA
Neuroimage 20:1064-75. 2003..These experimental results obtained in primate studies of striato-thalamo-cortico circuitry show a similar trend as hypothetized in Parkinson's disease-type degeneration... - Selective loss of 20S proteasome alpha-subunits in the substantia nigra pars compacta in Parkinson's diseaseKevin St P McNaught
Department of Neurology, Mount Sinai School of Medicine, Annenberg 14 73, One Gustave L Levy Place, New York, NY 10029, USA
Neurosci Lett 326:155-8. 2002..Thus, structural and function defects in 26/20S proteasomes may underlie protein accumulation, formation of proteinaceous Lewy bodies and dopaminergic neuronal death in the SNc in sporadic PD... - Cortico-hippocampal APP and NGF levels are dynamically altered by cholinergic muscarinic antagonist or M1 agonist treatment in normal miceHyemyung Seo
Neuroregeneration Laboratories, Harvard Medical School, McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
Eur J Neurosci 15:498-506. 2002.... - Generalized brain and skin proteasome inhibition in Huntington's diseaseHyemyung Seo
Neuroregeneration Laboratories, Departments of Neurology and Psychiatry, Harvard Medical School, McLean Hospital, Belmont, MA 02478, USA
Ann Neurol 56:319-28. 2004.... - Specific microRNAs modulate embryonic stem cell-derived neurogenesisAnna M Krichevsky
Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, USA
Stem Cells 24:857-64. 2006..We conclude that distinct miRNAs play a functional role in the determination of neural fates in ES cell differentiation... - Models of repair mechanisms for future treatment modalities of Parkinson's diseaseOle Isacson
Neuroregeneration Laboratories, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Brain Res Bull 57:839-46. 2002..Such neurons can be derived from stem cell sources or even stimulated to repair from endogenous stem cells. Novel molecular and cellular treatments provide new tools to prevent and alleviate Parkinson's disease... - Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and AChOle Isacson
Neuroregeneration Laboratory, McLean Hospital, Program in Neuroscience and Dept of Neurology, Harvard Medical School, Belmont, MA 02478 9106, USA
Trends Neurosci 25:79-84. 2002..This eventually leads to synaptic and dendritic loss with age... - High regulatability favors genetic selection in SLC18A2, a vesicular monoamine transporter essential for lifeZhicheng Lin
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
FASEB J 24:2191-200. 2010..These findings suggest that greater diversity of transcriptional regulations is the driving force for the haplotype selection in SLC18A2... - Herpes simplex virus/adeno-associated virus hybrid vectors for gene transfer to neurons. Preparation and useLauren C Costantini
Neuroregeneration Laboratory, Harvard Medical School, McLean Hospital, Belmont, MA, USA
Methods Mol Med 69:461-79. 2002 - Reducing amyloid plaque burden via ex vivo gene delivery of an Abeta-degrading protease: a novel therapeutic approach to Alzheimer diseaseMatthew L Hemming
Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
PLoS Med 4:e262. 2007..The objective of this study was to determine if enhancing the clearance of Abeta in the brain by ex vivo gene delivery of an Abeta-degrading protease can reduce amyloid plaque burden... - Neuroblast protuberances in the subventricular zone of the regenerative MRL/MpJ mouseKasey L Baker
Center for Regenerative Biology, University of Connecticut, Storrs, 06269, USA
J Comp Neurol 498:747-61. 2006.... - Spatial memory testing decreases hippocampal amyloid precursor protein in young, but not aged, female ratsHeather A Bimonte
Department of Physiology and Neuroscience and the Center for Studies on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
Neurosci Lett 328:50-4. 2002..Collectively, the data suggest that young and aged rats exhibit different relationships between APP and working memory, and that aged rats do not maintain the capacity to decrease APP in response to cognitive testing... - Altered proteasomal function in sporadic Parkinson's diseaseKevin St P McNaught
Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London Bridge, London SE1 1UL, UK
Exp Neurol 179:38-46. 2003..These findings suggest that failure of the ubiquitin-proteasome system to adequately clear unwanted proteins may underlie vulnerability and degeneration of the SNc in both sporadic and familial PD... - Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's diseaseIvar Mendez
Dalhousie University and Queen Elizabeth II Health Science Center, Division of Neurosurgery and Neuroscience, Halifax, Canada
Brain 128:1498-510. 2005.... - Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down's syndromeChristopher L Hunter
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA
Neurosci Res 45:437-45. 2003..These findings demonstrate that elevated APP and decreased NGF levels in limbic areas correlate with the progressive memory decline and cholinergic degeneration seen in middle-aged trisomic mice... - Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's diseaseMarius Wernig
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
Proc Natl Acad Sci U S A 105:5856-61. 2008..Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model... - Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 yearsIvar Mendez
Dalhousie University and Queen Elizabeth II Health Sciences Centre, Division of Neurosurgery and Department of Anatomy and Neurobiology, 1976 Summer Street, Halifax, Nova Scotia B3H 3A7, Canada
Nat Med 14:507-9. 2008..These findings are important for the understanding of the etiopathogenesis of midbrain dopamine neuron degeneration and future use of cell replacement therapies... - Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndromeAnn Charlotte Granholm
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Hippocampus 13:905-14. 2003..These findings demonstrate that estrogen can alleviate deficits in cholinergic and dendritic elements in the hippocampal formation and further strengthens the rationale to explore estrogen replacement therapy in women with DS... - Region-specific cell grafting into cervical and lumbar spinal cord in rat: a qualitative and quantitative stereological studyOsamu Kakinohana
Anesthesiology Research Laboratory, University of California-San Diego-0818, La Jolla, CA 92093, USA
Exp Neurol 190:122-32. 2004..Good survival of implanted cells for the three different cell lines used indicate that this grafting technique coupled with a systematic analysis of the individual grafting sites can represent a valuable implantation-analytical system... - Recent advances in cell-based therapy for Parkinson diseaseArnar Astradsson
NINDS Udall Parkinson s Disease Research Center of Excellence, Harvard University and McLean Hospital, Belmont, Massachusetts 02478, USA
Neurosurg Focus 24:E6. 2008..They conclude that recent advances in cell therapy for PD will create a viable long-term treatment option for synaptic repair for this debilitating disease... - Cell therapy and stem cells in animal models of motor neuron disordersEva Hedlund
Neuroregeneration Laboratory, Center for Neuroregeneration Research, McLean Hospital Harvard Medical School, Belmont, MA 02478, USA
Eur J Neurosci 26:1721-37. 2007..This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance... - Nociceptin/orphanin FQ receptor blockade attenuates MPTP-induced parkinsonismRiccardo Viaro
Department of Experimental and Clinical Medicine, Section of Pharmacology, University of Ferrara, Ferrara, Italy
Neurobiol Dis 30:430-8. 2008..We conclude that endogenous N/OFQ modulates motor activity in mice and nonhuman primates and contributes to parkinsonian symptoms in MPTP-treated animals. NOP receptor antagonists may represent a novel approach to Parkinson's disease...
Research Grants
- ANTI-INFLAMMATORY THERAPIES NEUROTOXICALLY INDUCED PDOle Isacson; Fiscal Year: 2004..Protection of the dopaminergic system by anti-inflammatory agents would be of tremendous therapeutic value for PD. ..
- TRANSGENIC XENOTRANSPLANTS FOR HUNTINGTON'S DISEASEOle Isacson; Fiscal Year: 2002..These experiments will improve our knowledge of basal ganglia function and plasticity, as well as determine parameters for optimal cell transplantation in patients with neurological disease. ..
- NEURONAL REPLACEMENT IN A MODEL OF HUNTINGTON'S DISEASEOle Isacson; Fiscal Year: 1993....