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CNR Research Articles

Parkinson's Disease

The Threshold Theory for Parkinson's Disease.
Engelender S. Isacson O.
Trends Neurosci., 2017Jan;40(1): 4-14, doi: 10.1016/j.tins.2016.10.008.
Abstract from PubMed
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In vivo modeling of neuronal function, axonal impairment and connectivity in neurodegenerative and neuropsychiatric disorders using induced pluripotent stem cells.
Korecka
et al.
Mol Cell Neurosci, 2015 • Dec. 10, 2015, doi: 10.1016/j.mcn.2015.12.004
Abstract from PubMed
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Glucocerebrosidase gene therapy prevents a-synucleinopathy of midbrain dopamine neurons.
Rocha et al.

Neurobiol Dis, 2015 • Sept. 25, 2015, doi: 10.1016/j.nbd.2015.09.009
Abstract from PubMed
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Fibroblast Biomarkers of Sporadic Parkinson's Disease and LRRK2 Kinase Inhibition.
Smith et al.

Mol Neurobiol, 2015 • Sept. 23, 2015, doi: 10.1007/s12035-015-9435-4
Abstract from PubMed
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Progressive decline of glucocerebrosidase in aging and Parkinson's disease.
Rocha et al. 

Ann Clin Transl Neurol, 2015 23(6), Apr. 2, 2015, doi: 10.1002/acn3.177
Abstract from PubMed
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Sustained Systemic Glucocerebrosidase Inhibition Induces Brain a-Synuclein Aggregation, Microglia and Complement C1q Activation in Mice.
Rocha et al.

Antioxidants & Redox Signaling, 2015 • 23(6), doi: 10.1089/ars.2015.6307
Abstract from PubMed
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A Nurr1 agonist causes neuroprotection in a Parkinson's disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C).
Smith et al.

PLoS One, 2015 • 10(3), Mar. 27, 2015, doi: 10.1371/journal.pone.0121072
Abstract from PubMed
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Successful function of autologous iPSC-derived dopamine neurons following transplantation in a non-human primate model of Parkinson's disease
Hallett et al.

Cell Stem Cell, 2015 • 16:269-274, Feb. 26, 2015, doi: 10.1016/j.stem.2015.01.018
Abstract from PubMed
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Long-term health of dopaminergic neuron transplants in Parkinson's disease patients
Hallett et al.

Cell Reports, 2014 • June 5, 2014, doi: 10.1016/j.celrep.2014.05.027
Abstract from PubMed
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Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection
McLean et al.

Neuroscience Letters, 2014 • 576:73-78
Abstract from PubMed
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LRRK2 mutations cause mitochrondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: Reversal by gene correction
Sanders et al.

Neurobiology of Disease, 2014 • 62:381-386
Abstract from PubMed
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Improved Cell Therapy Protocols for Parkinson's Disease Based on Differentiation Efficiency and Safety of hESC-, hiPSC, and Non-Human Primate iPSC-Derived Dopaminergic Neurons
Sundberg M et al.

Stem Cells, 2013 •31:1548-1562
Abstract from PubMed
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Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson's Disease
Cooper O et al.

Science Transl Med, July 4, 2012 • 4:401re90.
Abstract from PubMed
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Creation of an open-access, mutation-defined fibroblast resource for neurological disease research
Wray S et al.

PLoS One, Aug 27, 2012 • 7(8):e43099.
Abstract from PubMed
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The search for genetic mouse models of prodromal Parkinson's disease
Smith GA , Isacson O, Dunnet SB

Exp Neurol, July 14, 2012 • 237:267-273
Abstract from PubMed
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Alpha-synuclein overexpressing transgenic mice show internal organ pathology and autonomic deficits
Hallett PJ, McLean JR, Kartunen A, Langston JW, Isacson O

Neurobiol Dis, Apr 19, 2012 • 47:258-67.
Abstract from PubMed
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Viral and Inflammatory Triggers of Neurodegenerative Diseases.
Deleidi M, Isacson O.

Sci Transl Med, Feb 15, 2012 • 4:121-3.
Abstract from PubMed
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Characterization and criteria of embryonic stem and induced pluripotent stem cells for a dopamine replacement therapy
Cooper O, Parmar M, Isacson O

Prog Brain Res, 2012 •200:265-276
Abstract from PubMed
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Clinical translation of stem cells in neurodegenerative disorders.
Lindvall O, Barker RA, Brustle O, Isacson O, Svendsen CN.

Cell Stem Cell, Feb 3, 2012 • 10:151-5.
Abstract from PubMed

Using stem cells and iPS cells to discover new treatments for Parkinson's disease.
Cooper O, Hallett P, Isacson O.

Parkinsonism Relat Disord, Jan 18, 2012. Suppl 1:S14-6
Abstract from PubMed
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Transcript expression levels of full-length alpha-synuclein and its three alternatively spliced variants in Parkinson's disease brain regions and in a transgenic mouse model of alpha-synuclein overexpression.
McLean JR, Hallett PJ, Cooper O, Stanley M, Isacson O.
Mol Cell Neurosci, Dec 6, 2011 • 49(2):230-9.
Abstract from PubMed
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Oct4-induced reprogramming is required for adult brain neural stem cell differentiation into midbrain dopaminergic neurons.
Deleidi M, Cooper O, Hargus G, Levy A, Isacson O.
PLoS One; published online May 31, 2011 • 6(5): e19926
Abstract from PubMed
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Development of histocompatible primate induced pluripotent stem cells for neural transplantation.
Deleidi M, Hargus G, Hallett P, Osborn T, Isacson O.
Stem Cells, May 23, 2011 • 29(7):1052-63.
Abstract from PubMed
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Functions of the nigrostriatal dopaminergic synapse and the use of neurotransplantation in Parkinson's disease.
Tsui A, Isacson O.
The Journal of Neurology, August, 2011 • 258(8):1393-405.
Abstract from PubMed
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The Toll-Like receptor-3 agonist polyinosinic:polycytidylic acid triggers nigrostriatal dopaminergic degeneration.
Deleidi M, Hallett PJ, Koprich J, Chung CY, Isacson O.
Journal of Neuroscience; December 1, 2010 • 30(48): 16091- 101
Abstract from PubMed
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Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats.
Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E, Yow A, Soldner F, Hockemeyer D, Hallett PJ, Osborn T, Jaenisch R, Isacson O.
Proceedings of the National Academy of Sciences; September 2010 • 107: 15921- 6
Abstract from PubMed
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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 acid.
Cooper O, Hargus G, Deleidi M, Blak A, Osborn T, Marlow E, Lee K, Levy A, Perez-Torres E, Yow A, Isacson O.
Mol Cell Neurosci; July 2, 2010 • 45(3): 258- 66
Abstract from PubMed
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The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons.
Chung CY, Licznerski P, Alavian K, Simeone A, Lin Z, Martin E, Vance J, Isacson O.
Brain; June 23, 2010 • 1093/Brain/awq142 1-10
Abstract from PubMed
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Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway.
Chung S, Leung A, Han BS, Chang MY, Moon JI, Kim CH, Hong S, Pruszak J, Isacson O, Kim KS.
Cell Stem Cell; Dec. 4, 2009 • 5(6): 646- 58
Abstract from PubMed
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Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression.
Chung CY, Koprich J, Hallett P, Isacson O.
Proceedings of the National Academy of Sciences; Dec. 10, 2009 • 106: 22474- 79
Abstract from PubMed
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CD15, CD24 and CD29 define a surface biomarker code for neural lineage differentiation of stem cells.
Pruszak J, Ludwig W, Blak A, Alavian K, Isacson O.
Stem Cells; Sep. 1, 2009 • 27(12): 2928- 40
Abstract from PubMed
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Lack of functional relevance of isolated cell damage in transplants of Parkinson’s disease patients.
Cooper O, Astradsson A, Hallett P, Robertson H, Mendez I, Isacson O.
Journal of Neurology; August 27, 2009 • 256 (Suppl 3): 310- 16
Abstract from PubMed
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The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates--evidence from in vivo neuroimaging studies.
Astradsson A, Jenkins BG, Choi JK, Hallett PJ, Levesque MA, McDowell JS, Brownell AL, Spealman RD, Isacson O.
Neurobiological Disease; Sep 2009 • 35(3): 348- 51. Epub 2009 Jun 6
Abstract from PubMed
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Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy.
Chung CY, Koprich JB, Siddiqi H, Isacson O.
The Journal of Neuroscience; March 18, 2009 • 29(11): 3365- 73
Abstract from PubMed
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Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors.
Soldner F, Hockemeyer D, Beard C, Gao Q, Bell G, Cook E, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R
Cell; March 6, 2009 • 136, 964- 977
Abstract from PubMed
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PSD-95 Uncouples Dopamine-Glutamate Interaction in the D1/PSD-95/NMDA Receptor Complex.
Zhang J, Xu T, Hallett P, Watanabe M, Grant S, Isacson O, and Yao W
The Journal of Neuroscience; March 4, 2009 • 29(9): 2948- 60
Abstract from PubMed
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Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeutics.
Lin L, Lesnick TG, Maraganore DM, Isacson O
Trends in Neuroscience; January 21, 2009 • 32(3): 142- 9
Abstract from PubMed
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Implanted reuptake-deficient or wild-type dopaminergic neurons improve ON L-dopa dyskinesias without OFF-dyskinesias in a rat model of Parkinson's disease.
Vinuela A, Hallett P, Reske-Nielsen C, Patterson M, Sotnikova T, Caron M, Gainetdinov R, Isacson O
Brain; Nov 6 2008 • 131(12): 3361- 79
Abstract from PubMed
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Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson's disease.
Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, Isacson O
Brain; Aug. 2008 • 131(Pt 8): 2127- 39
Abstract from PubMed
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Enhanced Binding of Metabotropic Glutamate Receptor Type 5 (mGluR5) PET Tracers in the Brain of Parkinsonian Primates.
Sanchez-Pernaute R, Wang JQ, Kuruppu D, Cao L, Tueckmantel W, Kozikowski A, Isacson O, Brownell AL
Neuroimage; August 1, 2008 • 42(1): 248- 51. Epub April 20, 2008
Abstract from PubMed
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Nociceptin/orphanin FQ Receptor Blockade Attenuates MPTP-induced Parkinsonism.
Viaro R, Sanchez-Pernaute R, Marti M, Trapella C, Isacson O, Morari M
Neurobiology of Disease; June 2008 • 30(3): 430- 8. Epub March 8, 2008
Abstract from PubMed
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Fate Mapping and Lineage Analyses Demonstrate the Production of a Large Number of Striatal Neuroblasts after TGF{alpha} and Noggin Striatal Infusions into the Dopamine-depleted Striatum
De Chevigny A, Cooper O, Vinuela A, Reske-Nielsen C, Lagace DC, Eisch AJ, Isacson O
Stem Cells; June 12, 2008 • 26: 2349– 60
Abstract from PubMed
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Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years
Mendez I, Viñuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski J, Isacson O
Nature Medicine; Published online: April 6, 2008 • 14(5): 507- 9
Abstract from PubMed
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Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease
Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R
Proceedings of the Natl. Academy of Science; Published online April, 2008 •
Abstract from PubMed
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Embryonic Stem (ES) Cell-derived Pitx3-eGFP Midbrain Dopamine Neurons Survive Enrichment by FACS and Function in an Animal Model of Parkinson's Disease
Hedlund E, Pruszak J, Lardaro T, Ludwig W, Viñuela A, Kim K, Isacson O
Stem Cells; First published online April 3, 2008
Abstract from PubMed
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Recent advances in cell-based therapy for Parkinson disease
Astradsson A, Cooper O, Viñuela A, Isacson O
Neurosurg Focus; January 1, 2008 • 24(3-4): E6
Abstract from PubMed
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Neuroinflammation mediated by IL-1 beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson's disease
Koprich J, Reske-Nielsen C, Mithal P, Isacson O
JNeuroinflammation; February 27, 2008; 5(1): 8
Abstract from PubMed
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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 neurons
Hong S, Kang UJ, Isacson O, Kim KS
J. Neurochem., Jan. 2008; 104(2):316-24. Epub Oct. 18, 2007
Abstract from PubMed
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Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease
Redmond D, Viñuela A, Kordower JH, Isacson O
Neurobiology of Disease, Jan. 2008; 29(1):103-16. Epub Aug. 28, 2007
Abstract from PubMed
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Inhibition of the leucine-rich repeat protein LINGO-1 enhances survival, structure, and function of dopaminergic neurons in Parkinson's disease models
Inoue H, Lin L, Lee X, Shao Z, Mendes S, Snodgrass-Belt P, Sweigard H, Engber T, Pepinsky B, Yang L, Beal MF, Mi S, Isacson O
Published online in Proc. Natl. Acad. Sci. August 28, 2007
Abstrac from PubMed
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An Endogenous Serine/Threonine Protein Phosphatase Inhibitor, G-Substrate, Reduces Vulnerability in Models of Parkinson's Disease
Chung CY, Koprich J, Endo S, Isacson O
J. Neurosci. Aug. 1, 2007
Abstract from PubMed
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In vivo evidence of D(3) dopamine receptor sensitization in parkinsonian primates and rodents with l-DOPA-induced dyskinesias
Sanchez-Pernaute R, Jenkins BG, Choi JK, Chen YC, Isacson O
Neurobiol Dis., May 2007
Abstract from PubMed
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Markers and Methods for Cell Sorting of Human Embryonic Stem Cell-derived Neural Cell Populations
Pruszak J, Sonntag KC, Aung MH, Sanchez-Pernaute R, Isacson O
Stem Cells, June 2007
Abstract from PubMed
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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 populations
Hedlund E, Pruszak J, Ferree A, Viñuela A, Hong S, Isacson O, Kim K
Stem Cells, May 2007
Abstract from PubMed
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Inhibition of the dopamine D1 receptor signaling by PSD-95
Zhang J, Viñuela A, Neely M, Hallett P, Grant S, Miller G, Isacson O, Caron M, and Yao W
J. Biol. Chem., March 16, 2007
Abstract from PubMed
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ES cell-derived neuroepithelial cell cultures
Karki S, Pruszak J, Isacson O, Sonntag K
JoVE, Issue 1, Dec. 2006
Link to Video Article

Transplanted dopamine neurons derived from primate ES cells preferentially innervate DARPP-32 striatal progenitors within the graft
Ferrari D, Sanchez-Pernaute R, Lee H, Studer L, Isacson O
Eur. J. Neurosci. October 2006
Abstract from PubMed
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Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the BMP antagonist noggin
Sonntag KC, Pruszak J, Yoshizaki T, Van Arensbergen J, Sanchez-Pernaute R, Isacson O
Stem Cells; February 2007
Abstract from PubMed
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Neuroblast protuberances in the subventricular zone of the regenerative MRL/MpJ mouse
Baker KL, Daniels SB, Lennington JB, Lardaro T, Czap A, Notti RQ, Cooper O, Isacson O, Frasca S Jr, Conover JC
J Comp Neurol. Aug 22, 2006
Abstract from PubMed
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A tyrosine hydroxylase-yellow fluorescent protein knock-in reporter system labeling dopaminergic neurons reveals potential regulatory role for the first intron of the rodent tyrosine hydroxylase gene
Kelly BB, Hedlund E, Kim C, Ishiguro H, Isacson O, Chikaraishi DM, Kim KS, Feng G
Published in Neuroscience on July 28, 2006
Abstract from PubMed
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Axonal growth regulation of fetal and ES-derived dopaminergic neurons by Netrin-1 and Slits
Lin L, Isacson O
Stem Cells; July 2006
Abstract from PubMed
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Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation
Chung S, Shin BS, Hedlund E, Pruszak J, Ferree A, Kang UJ, Isacson O, Kim KS
J Neurochem. June 2006
Abstract from PubMed
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Stromal cell-derived inducing activity, Nurr1 and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells
Kim DW, Chung S, Hwang M, Ferree A, Tsaia HC, Park JJ, Chung S, Namc TS, Kang UJ, Isacson O, Kim KS
Stem Cells; March 2006
Abstract from PubMed
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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 vitro
Chung S, Shin BS, Hwang M, Lardaro T, Kang UJ, Isacson O, Kim KS
Stem Cells; March 16, 2006
Abstract from PubMed
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Specific microRNAs modulate ES cell-derived neurogenesis
Krichevsky AM, Sonntag KC, Isacson O, Kosik KS
Stem Cells Vol. 24 No. 4 April 2006, pp. 857-864
Abstract from PubMed
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Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging
Sanchez-Pernaute R, Brownell AL, Jenkins BG, Isacson O.
Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):251-6.
Abstract from PubMed
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Long-term survival of dopamine neurons derived from parthenogenetic primate embryonic stem cells (Cyno1) after transplantation
Sanchez-Pernaute R, Studer L, Ferrari D, Perrier A, Lee H, Viñuela A, Isacson O.
Stem Cells. 2005 Jun 7
Abstract from PubMed
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Cell type specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection
Chung CY, Seo H, Sonntag KC, Brooks A, Lin L, Isacson O.
Hum. Mol. Genet. 2005; 14: 1709-1725.
Abstract from PubMed
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Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease
Mendez I, Sanchez-Pernaute R, Cooper O, Viñuela A, Ferrari D, Björklund L, Dagher A, and Isacson O.
Brain 2005 128(7):1498-1510
Abstract from PubMed
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Stem cells may reshape the prospect of Parkinson's disease therapy
Sonntag KC, Simantov R, Isacson O.
Brain Res Mol Brain Res. 2005 Mar 24;134(1):34-51.
Abstract from PubMed
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Netrin-1 and slit-2 regulate and direct neurite growth of ventral midbrain dopaminergic neurons
Lin L, Rao Y and Isacson O.
Mol Cell Neurosci. 2005 Mar;28(3):547-55.
Abstract from PubMed
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Context-dependent neuronal differentiation and germ layer induction of Smad4-/- and Cripto-/- embryonic stem cells
Sonntag KC, Simantov R, Björklund L, Cooper O, Pruszak J, Kowalke F, Gilmartin J, Ding J, Hu YP, Shen MM and Isacson O
Mol Cell Neurosci. 2005 Mar;28(3):417-29.
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The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons
Chung S, Hedlund E, Hwang M, Kim DW, Shin BS, Hwang DY, Jung Kang U, Isacson O, Kim KS.
Mol Cell Neurosci. 2005 Feb;28(2):241-52.
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Mapping dopamine function in primates using pharmacologic magnetic resonance imaging
Jenkins BG, Sanchez-Pernaute R, Brownell AL, Chen YI and Isacson O.
J. Neurosci., Oct 27, 2004, 24(43):9553-9560
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Intrastriatal transforming growth factor delivery to a model of Parkinson's disease induces proliferation and migration of endogenous adult neural progenitor cells without differentiation into dopaminergic neurons
Cooper, O. and Isacson, O.
J. Neurosci., Oct 13, 2004, 24(41):8924-8931
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Problems and solutions for circuits and synapses in Parkinson's disease
Isacson, O.
Neuron. 2004 Jul 22;43(2):165-8
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Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease.
Sánchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell AL and Isacson O.
Journal of Neuroinflammation 2004, 1:6
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Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiation.
Sonntag KC, Simantov R, Kim KS, Isacson, O.
Eur. J. Neurosci. 2004 19, 1141-1152.
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Mapping of brain function after MPTP-induced neurotoxicity in a primate Parkinson's disease model.
Brownell AL, Canales K, Chen YI, Jenkins BG, Owen C, Livni E, Yu M, Cicchetti F, Sanchez-Pernaute R, Isacson O.
Neuroimage. 2003 Oct;20(2):1064-75.
Abstract from PubMed
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The production and use of cells as therapeutic agents in neurodegenerative diseases.
Isacson O.

Lancet Neurology 2003 Jul;2(7):417-24.
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Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner.
Kim KS, Kim CH, Hwang DY, Seo H, Chung S, Hong SJ, Lim JK, Anderson T, Isacson O.

J Neurochem 2003 May;85(3):622-34.

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Toward full restoration of synaptic and terminal function of the dopaminergic system in Parkinson's disease by stem cells.
Isacson O, Bjorklund LM, Schumacher JM.
Ann Neurol 2003;53(3 Suppl 1):S135-48.
Parkinson's disease Special Annals of Neurology Issue:
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Immune parameters relevant to neural xenograft survival in the primate brain.
Cicchetti F, Fodor W, Deacon TW, Van Horne C, Rollins S, Burton W, Costantini LC, Isacson O.
Xenotransplantation 2003 Jan;10(1):41-9.
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Altered proteasomal function in sporadic Parkinson's disease.
St P McNaught K, Belizaire R, Isacson O, Jenner P, Olanow CW.
Exp Neurol 2003 Jan;179(1):38-46.
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Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons.
Chung, S., Sonntag, K-C., Andersson, T., Bjorklund, L.M., Park, J.-J., Kim, D-W., Kang, U.J., Isacson, O., Kim, K.-S.
Eur. J. Neurosci. 2002 16, 1829-1838.
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Combined inhibition of apoptosis and complement improves neural graft survival of embryonic rat and porcine mesencephalon in the rat brain.
Cicchetti F, Costantini L, Belizaire R, Burton W, Isacson O, Fodor W.
Exp Neurol 2002; 177, 376-84
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Functional Imaging of the Dopamine System: In Vivo Evaluation of Dopamine Deficiency and Restoration
Sánchez-Pernaute R, Brownell A-L, Isacson O
Neurotoxicology 2002 vol 23, 469-478

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Selective loss of 20S proteasome alpha-subunits in the substantia nigra pars compacta in Parkinson's disease.
McNaught KS, Belizaire R, Jenner P, Olanow CW, Isacson O
Neurosci Lett 2002 Jul 5;326(3):155-8
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Models of repair mechanisms for future treatment modalities of Parkinson's disease.
Isacson O
Brain Res Bull 2002 Apr;57(6):839-46
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Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats
monitored by immunohistochemistry and PET imaging.

Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E and Isacson O
Eur. J. Neurosci. 2002 15, 991-998
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Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model.
Björklund L, Pernaute RS, Chung S, Andersson T, Chen IYC, McNaught KSP, Brownell AL, Jenkins BG, Wahlestedt C, Kim KS, Isacson O
Proc Natl Acad Sci U S A. 2002 Feb 19;99(4):2344-2349.
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Parkinsonian Motor Deficits Are Reflected by Proportional A9/A10 Dopamine Neuron Degeneration in the Rat.
Moore AE, Cicchetti F, Hennon J, Isacson O.
Experimental Neurology 2001 Dec;172(2): 363- 76
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Failure of the ubiquitin-proteasome system in Parkinson's disease.
McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P.
Nat Rev Neurosci 2001 Aug; 2(8): 589- 94

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Cell implantation therapies for Parkinson's disease using neural stem, transgenic or xenogeneic donor cells.
Isacson O, Costantini L, Schumacher JM, Cicchetti F, Chung S, Kim K
Parkinsonism Relat. Disord. 2001 Jul; 7(3): 205- 12
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Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease.
Costantini LC, Cole D, Chaturvedi P, Isacson O
Eur J Neurosci 2001 Mar;13(6):1085-92
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Immunophilin ligands and GDNF enhance neurite branching or elongation from developing dopamine neurons in culture.
Costantini LC, Isacson O
Exp Neurol; Jul 2000; 164(1): 60- 70
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Dopamine imaging markers and predictive mathematical models for progressive degeneration in Parkinson's disease.
Brownell AL, Jenkins BG, Isacson O
Biomed Pharmacother; Apr
1999; 53(3): 131- 40
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Combined PET/MRS brain studies show dynamic and long-term physiological changes in a primate model of Parkinson disease.
Brownell AL, Jenkins BG, Elmaleh DR, Deacon TW, Spealman RD, Isacson O
Nat Med; Nov 1998; 4(11): 1308- 12
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Blastula-stage stem cells can differentiate into dopaminergic and serotonergic neurons after transplantation.
Deacon T, Dinsmore J, Costantini LC, Ratliff J, Isacson O
Exp Neurol; Jan
1998; 149(1): 28- 41
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Neural transplantation studies reveal the brain's capacity for continuous reconstruction.
Isacson O, Deacon T
Trends Neurosci; Oct 1997; 20(10): 477- 82

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Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease.
Deacon T, Schumacher J, Dinsmore J, Thomas C, Palmer P, Kott S, Edge A, Penney D, Kassissieh S, Dempsey P, Isacson O Nat Med 1997 Mar; 3(3): 350-3
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Huntington's Disease

Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175KI mouse model of Huntington's disease
Smith et al.
Human Molecular Genetics, April 30, 2014. 10.1093/hmg/ddu166
Abstract from PubMed
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No evidence for disease-like processes in fetal transplants.
Hallett P, Cooper O, Isacson O
PNAS, Sep 2009; 10.1073/pnas.0908169106.
Abstract from PubMed
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Compensatory changes in the ubiquitin-proteasome system, BDNF and mitochondrial complex II / III in YAC72 and R6/2 transgenic mice partially model Huntington's disease (HD) patients.
Seo H, Kim W, Isacson O
Human Molecular Genetics July 17, 2008. 10.1093/hmg/ddn211
Abstract from PubMed
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Proteasome Activator Enhances Survival of Huntington's Disease Neuronal Model Cells.
Seo H, Sonntag KC, Kim W, Cattaneo E, Isacson O.
PLoS ONE February 2007
Abstract from PubMed
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What are the long-term effects of neural grafting in patients with Huntington's disease?
Isacson O.
Nat Clin Pract Neurol. Sept 2006
Abstract from PubMed
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Generalized brain and skin proteasome inhibition in Huntington's disease.
Hyemyung Seo, PhD, Kai-Christian Sonntag, MD, PhD, Ole Isacson, MD, DMSc
Annals of Neurology; Sept 2004
Abstract from PubMed
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The production and use of cells as therapeutic agents in neurodegenerative diseases.
Isacson O.

Lancet Neurol. 2003 Jul;2(7):417-24
Abstract from PubMed
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Neurotrophic factors NGF and FGF-2 alter levels of huntingtin (IT15) in striatal neuronal cell cultures.
Haque NS and Isacson O
Cell Transplant 2000 Sep-Oct;9(5):623-7
Abstract from PubMed

Transplanted fetal striatum in Huntington's disease: phenotypic development and lack of pathology.
Freeman TB, Cicchetti F, Hauser RA, Deacon TW, Li XJ, Hersch SM, Nauert GM, Sanberg PR, Kordower JH, Saporta S, Isacson O Proc Natl Acad Sci U S A 2000 Dec 5;97(25):13877-82
Abstract from PubMed

Therapeutic strategies for Huntington's disease based on a molecular understanding of the disorder.
Haque NS, Borghesani P, Isacson O
Mol Med Today 1997 Apr;3(4):175-83

Abstract from PubMed

Antisense gene therapy for neurodegenerative disease?
Haque N, Isacson O
Exp Neurol 1997 Mar;144(1):139-46
Abstract from PubMed

Gene transfer to the nigrostriatal system by hybrid herpes simplex virus/adeno-associated virus amplicon vectors.
Costantini LC, Jacoby DR, Wang S, Fraefel C, Breakefield XO, Isacson O
Hum Gene Ther 1999 Oct 10;10(15):2481-94
Abstract from PubMed

Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres.
Isacson O, Deacon TW, Pakzaban P, Galpern WR, Dinsmore J, Burns LH
Nat Med 1995 Nov;1(11):1189-94
Abstract from PubMed

NGF attenuates 3-nitrotyrosine formation in a 3-NP model of Huntington's disease.
Galpern WR, Matthews RT, Beal MF, Isacson O
Neuroreport 1996 Nov 4;7(15-17):2639-42
Abstract from PubMed

Alzheimer's, ALS and Other Neurodegenerative Diseases

Widespread neuron-specific transgene expression in brain and spinal cord following synapsin promoter-driven AAV9 neonatal intracerebroventricular injection
McLean et al.

Neuroscience Letters, 2014 •576:73-78
Abstract from PubMed
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The hAPP-YAC transgenic model has elevated UPS activity in the frontal cortex similar to Alzheimer's disease and Down's syndrome.
Seo H, Isacson O.
Journal of Neurochemistry; July 13, 2010. [Epub ahead of print].
Abstract from PubMed
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Global gene expression profiling of somatic motor neuron populations with different vulnerability identify molecules and pathways of degeneration and protection.
Hedlund E, Karlsson M, Osborn T, Ludwig W, Isacson O.
Brain; Aug 2010. 133: 2313 - 30.
Abstract from PubMed
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ALS Model Glia Can Mediate Toxicity to Motor Neurons Derived from Human Embryonic Stem Cells.
Hedlund E, Isacson O.
Cell Stem Cell; 2008 Dec 4. 3(6):575 - 6.
Abstract from PubMed
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Cell therapy and stem cells in animal models of motor neuron disorders.
Hedlund E, Hefferan M, Marsala M, Isacson O.
European Journal of Neuroscience; Vol. 26, pp. 1721 - 37, 2007.
Abstract from PubMed
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Reducing Amyloid Plaque Burden via Ex Vivo Gene Delivery of an AB-Degrading Protease: A Novel Therapeutic Approach to Alzheimer Disease
Hemming M, Patterson M, Reske-Nielsen C, Lin L, Isacson O, Selkoe D
PLoS Med. 2007 August; 4(8): e262.
Abstract from PubMed
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Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice.
Seo H and Isacson O
Exp Neurol. 2005 Jun;193(2):469-80.
Abstract from PubMed
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Region-specific cell grafting into cervical and lumbar spinal cord in rat: a qualitative and quantitative stereological study.
Kakinohana O, Cizkova D, Tomori Z, Hedlund E, Marsala S, Isacson O, Marsala M.
Exp Neurol. 2004 Nov;190(1):122-32.
Abstract from PubMed
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Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome.
Granholm AC, Sanders L, Seo H, Lin L, Ford K, Isacson O.
Hippocampus. 2003;13(8):905-14.

Abstract from PubMed
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The production and use of cells as therapeutic agents in neurodegenerative diseases.
Isacson O.
Lancet Neurol. 2003 Jul;2(7):417-24.
Abstract from PubMed
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Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down's syndrome.
Hunter CL, Isacson O, Nelson M, Bimonte-Nelson H, Seo H, Lin L, Ford K, Kindy MS, Granholm AC.
Neurosci Res 2003 Apr;45(4):437-45
Abstract from PubMed
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Spatial memory testing decreases hippocampal amyloid precursor protein in young, but not aged, female rats.
Bimonte HA, Granholm AC, Seo H, Isacson O.
Neurosci Lett 2002 Aug 2;328(1):50-4
Abstract from PubMed

Alzheimer's disease and Down's syndrome: roles of APP, trophic factors and ACh.
Isacson O, Seo H, Lin L, Albeck D, Granholm AC.
Trends Neurosci 2002 Feb;25(2):79-84
Abstract from PubMed
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Cortico-hippocampal APP and NGF levels are dynamically altered by cholinergic muscarinic antagonist or M1 agonist treatment in normal mice.
Seo H, Ferree AW, Isacson O.
Eur J Neurosci 2002 Feb;15(3):498-506
Abstract from PubMed
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Selective Antibody-Induced Cholinergic Cell and Synapse Loss Produce Sustained Hippocampal and Cortical Hypometabolism with Correlated Cognitive Deficits
Browne SE, Lin L, Mattsson A, Georgievska B, Isacson O

Experimental Neurology July 2001, Vol. 170, No. 1: 36-47
Abstract from PubMed
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Cognitive changes and modified processing of amyloid precursor protein in the cortical and hippocampal system after cholinergic synapse loss and muscarinic receptor activation.
Lin L, Georgievska B, Mattsson A, Isacson O
Proc Natl Acad Sci U S A; 1999 Oct 12; 96(21): 12108- 13

Abstract from PubMed

Morris water maze analysis of 192-IgG-saporin-lesioned rats and porcine cholinergic transplants to the hippocampus.
LeBlanc CJ, Deacon TW, Whatley BR, Dinsmore J, Lin L, Isacson O
Cell Transplant 1999 Jan-Feb; 8(1): 131- 42

Abstract from PubMed

Pig fetal septal neurons implanted into the hippocampus of aged or cholinergic deafferented rats grow axons and form cross-species synapses in appropriate target regions.
Deacon T, Whatley B, LeBlanc C, Lin L, Isacson O
Cell Transplant 1999 Jan-Feb;8(1):111-29

Abstract from PubMed

Chronic cognitive deficits and amyloid precursor protein elevation after selective immunotoxin lesions of the basal forebrain cholinergic system.
Lin L, LeBlanc CJ, Deacon TW, Isacson O

Neuroreport 1998 Feb 16;9(3):547-52

Abstract from PubMed

Excitotoxic lesions of the rat entorhinal cortex. Effects of selective neuronal damage on acquisition and retention of a non-spatial reference memory task.
Levisohn LF, Isacson O
Brain Res 1991 Nov 15;564(2):230-44

Abstract from PubMed



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