Research Topics
Genomes and Genes
| Jie ShenSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
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Detail Information
Publications
Impaired neurotransmitter release in Alzheimer's and Parkinson's diseasesJie Shen
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA, USA
Neurodegener Dis 7:80-3. 2010..Together, our genetic studies suggest that presynaptic dysfunction might be a converging early pathogenic event before neurodegeneration in AD and PD...- Brain region specific mitophagy capacity could contribute to selective neuronal vulnerability in Parkinson's diseaseMadeleine Diedrich
Institute for Medical Genetics and Human Genetics, Charite Universitatsmedizin Berlin, D 13353 Berlin, Germany
Proteome Sci 9:59. 2011..Taken together, the delicate balance between oxidative protection and mitophagy capacity in different brain regions could contribute to brain region-specific pathological patterns in PD... - The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanismJie Shen
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:403-9. 2007..We also speculate that Abeta42 may act primarily to antagonize PS-dependent functions, possibly by operating as an active site-directed inhibitor of gamma-secretase... - Presenilins are required for maintenance of neural stem cells in the developing brainWoo Young Kim
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA, 02115, USA
Mol Neurodegener 3:2. 2008..These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development... - Mitochondria and dopamine: new insights into recessive parkinsonismJie Shen
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Neuron 43:301-4. 2004..This review will summarize recent advances in our understanding of these gene products, with emphasis on the surprising convergence of their functions... - Impaired dopamine release and synaptic plasticity in the striatum of parkin-/- miceTohru Kitada
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurochem 110:613-21. 2009.... - Inactivation of presenilins causes pre-synaptic impairment prior to post-synaptic dysfunctionDawei Zhang
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA
J Neurochem 115:1215-21. 2010.... - Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout miceTohru Kitada
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusets, USA
J Neurochem 111:696-702. 2009..These findings also support the notion that mammalian Parkin and PINK1 may function in the same genetic pathway as in Drosophila... - Presenilins are essential for regulating neurotransmitter releaseChen Zhang
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
Nature 460:632-6. 2009.... - R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in miceYouren Tong
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 106:14622-7. 2009..Together, our data suggest that the R1441C mutation in LRRK2 impairs stimulated dopamine neurotransmission and D2 receptor function, which may represent pathogenic precursors preceding dopaminergic degeneration in PD brains... - Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1Matthew S Goldberg
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
Neuron 45:489-96. 2005..Furthermore, DJ-1(-/-) mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions... - Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stressClement A Gautier
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 105:11364-9. 2008.... - Hippocampal spatial memory impairments caused by the familial Alzheimer's disease-linked presenilin 1 M146V mutationXiaoyan Sun
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Neurodegener Dis 2:6-15. 2005.... - Conditional inactivation of presenilin 1 prevents amyloid accumulation and temporarily rescues contextual and spatial working memory impairments in amyloid precursor protein transgenic miceCarlos A Saura
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 25:6755-64. 2005..These results reveal that in vivo reduction of Abeta via the inactivation of PS1 effectively prevents amyloid-associated neuropathological changes and can, but only temporarily, improve cognitive impairments in APP transgenic mice... - Characterization of age-dependent and progressive cortical neuronal degeneration in presenilin conditional mutant miceMary Wines-Samuelson
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
PLoS ONE 5:e10195. 2010.... - Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient miceTohru Kitada
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 104:11441-6. 2007..These results reveal a critical role for PINK1 in DA release and striatal synaptic plasticity in the nigrostriatal circuit and suggest that altered dopaminergic physiology may be a pathogenic precursor to nigrostriatal degeneration... - Notch1 signaling influences v2 interneuron and motor neuron development in the spinal cordXudong Yang
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Dev Neurosci 28:102-17. 2006..These results provide support for a role of Notch1 in neuronal subtype specification in the ventral spinal cord... - Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out miceVassilios Beglopoulos
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 279:46907-14. 2004..These results indicate that the memory impairment and neurodegeneration in PS cDKO mice are not caused by Abeta accumulation and that loss of PS function leads to differential up-regulation of inflammatory markers in the cerebral cortex... - Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged miceYouren Tong
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Proc Natl Acad Sci U S A 107:9879-84. 2010.... - Parkin protects against mitochondrial toxins and beta-amyloid accumulation in skeletal muscle cellsKenneth M Rosen
Department of Neurology, Caritas St Elizabeth s Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA
J Biol Chem 281:12809-16. 2006..These data support the hypothesis that in myocytes parkin has dual properties in the maintenance of skeletal muscle mitochondrial homeostasis and in the regulation of A beta levels... - CREB binding protein is required for both short-term and long-term memory formationGuiquan Chen
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA
J Neurosci 30:13066-77. 2010..Collectively, these findings suggest a crucial role for CBP in the formation of both short- and long-term memory... - alpha-synuclein and LRRK2: partners in crimeYouren Tong
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA, 02115, USA
Neuron 64:771-3. 2009..The results reveal an interesting interaction between alpha-synuclein and LRRK2, two gene products linked to dominantly inherited Parkinson's disease... - A presenilin-1 mutation identified in familial Alzheimer disease with cotton wool plaques causes a nearly complete loss of gamma-secretase activityElizabeth A Heilig
Center for Human Genetic Research and Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
J Biol Chem 285:22350-9. 2010..Rather, our findings provide support for the hypothesis that pathogenic mutations cause a general loss of presenilin function... - Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null miceAlexander Shtifman
Department of Neurology, Caritas St Elizabeth s Medical Center, Tufts University School of Medicine, 736 Cambridge St, CBR 406, Boston, MA 02135, USA
Neurobiol Aging 32:125-32. 2011..These results provide evidence of DJ-1's association with Ca(2+) regulatory pathways in mouse skeletal muscle, and suggest the potential benefit of resveratrol to functionally compensate for the loss of DJ-1... - Presenilins in the developing, adult, and aging cerebral cortexMary Wines-Samuelson
Center for Neurologic Diseases, Brigham and Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, Massachussetts 02115, USA
Neuroscientist 11:441-51. 2005..These diverse functions of presenilins in cortical development and function and neuronal survival have important implications for the pathogenesis of neurodegenerative dementia... - Mitochondrial dysfunction and oxidative damage in parkin-deficient miceJames J Palacino
Center for Neurologic Diseases, Brigham and Women s Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 279:18614-22. 2004.... - Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegenerationCarlos A Saura
Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Neuron 42:23-36. 2004..These results define essential roles and molecular targets of presenilins in synaptic plasticity, learning and memory, and neuronal survival in the adult cerebral cortex... - Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathwayXudong Yang
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
Dev Biol 269:81-94. 2004..Together, these complementary gain-of-function and loss-of-function studies reveal a previously unappreciated role of Notch signaling in the regulation of apoptotic cell death during early mammalian neural development... - Regulation of CRE-dependent transcription by presenilins: prospects for therapy of Alzheimer's diseaseVassilios Beglopoulos
Center for Neurologic Diseases, Brigham and Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Trends Pharmacol Sci 27:33-40. 2006..Thus, modulation of CRE-dependent transcription might be beneficial for the treatment of dementia in AD... - Indirect regulation of presenilins in CREB-mediated transcriptionHirotaka Watanabe
Center for Neurologic Diseases, Brigham and Women s Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 284:13705-13. 2009.... - Role of presenilin-1 in cortical lamination and survival of Cajal-Retzius neuronsMary Wines-Samuelson
Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
Dev Biol 277:332-46. 2005..These findings show a cell-autonomous role for PS1 in cortical lamination and radial glial development, and a non-cell-autonomous role for PS1 in CR neuron survival... - Increased DJ-1 expression under oxidative stress and in Alzheimer's disease brainsStephanie Baulac
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Harvard University, Boston, MA 02115, USA
Mol Neurodegener 4:12. 2009..Therefore, our results strongly suggest that DJ-1 expression is not necessary during zebrafish development but can be induced in zebrafish exposed to oxidative stress and is present in human AD brains... - A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiationYue Yang
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
Science 326:575-8. 2009..Thus, our findings define a Cdc20-APC ubiquitin signaling pathway that governs presynaptic development, which holds important implications for neuronal connectivity and plasticity in the brain... - Cambogin is preferentially cytotoxic to cells expressing PDGFRZe Tian
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
PLoS ONE 6:e21370. 2011..These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB... - Loss of leucine-rich repeat kinase 2 causes age-dependent bi-phasic alterations of the autophagy pathwayYouren Tong
Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Mol Neurodegener 7:2. 2012..We previously reported that loss of LRRK2 causes impairment of protein degradation pathways as well as increases of apoptotic cell death and inflammatory responses in the kidney of aged mice... - A nasal proteosome adjuvant activates microglia and prevents amyloid depositionDan Frenkel
Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
Ann Neurol 63:591-601. 2008.... - Gene-targeting technologies for the study of neurological disordersVassilios Beglopoulos
Center for Neurologic Diseases, Brigham and Women's Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
Neuromolecular Med 6:13-30. 2004..The importance of the results obtained by these models for the understanding of the pathogenic mechanism underlying the disorders is discussed... - Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cellsZe Tian
Children s Hospital Informatics Program at Harvard MIT Division of Health Sciences and Technology, Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
Int J Cancer 122:31-8. 2008..Dulxanthone A is therefore likely a promising preventive and/or therapeutic agent against Hepatoma... - Spectrum of heart disease associated with murine and human GATA4 mutationSatish K Rajagopal
Department of Cardiology, Children s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
J Mol Cell Cardiol 43:677-85. 2007..Additional studies will be required to determine the degree to which GATA4 mutation contributes to human CHD characterized by ECD or RV hypoplasia... - Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neuronsMatthew S Goldberg
Center for Neurologic Diseases, Harvard Medical School, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
J Biol Chem 278:43628-35. 2003..Together these findings provide the first evidence for a novel role of parkin in dopamine regulation and nigrostriatal function, and a non-essential role of parkin in the survival of nigral neurons in mice... - Protein kinases linked to the pathogenesis of Parkinson's diseaseJie Shen
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Neuron 44:575-7. 2004..The LRRK2 gene is predicted to encode a large protein containing leucine-rich repeats and Ras/GTPase, tyrosine kinase-like, and WD40 domains... - [Preliminary study on biological behavior and staging of transplanted hepatoma in rats]Wei Gu
Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Zhong Xi Yi Jie He Xue Bao 3:136-8. 2005..To establish a staging standard for a transplanted hepatoma model in rats, which may be equivalent to the human primary liver cancer... - Characterization of the reconstituted gamma-secretase complex from Sf9 cells co-expressing presenilin 1, nicastrin [correction of nacastrin], aph-1a, and pen-2Lili Zhang
Department of Neurobiology, Schering Plough Research Institute, Kenilworth, New Jersey 07033, USA
Biochemistry 44:4450-7. 2005..These studies may provide important insight into the development of a new generation of selective gamma-secretase inhibitors with an improved side effect profile... - gamma-secretase functions through Notch signaling to maintain skin appendages but is not required for their patterning or initial morphogenesisYonghua Pan
Department of Molecular Biology and Pharmacology, Division of Dermatology, Washington University School of Medicine, Box 8103, 660 South Euclid Avenue, St Louis, MO 63110, USA
Dev Cell 7:731-43. 2004.... - Effect of presenilins in the apoptosis of thymocytes and homeostasis of CD8+ T cellsAntonio Maraver
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 1st Avenue, New York, NY 10016, USA
Blood 110:3218-25. 2007.... - Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLPRaphaelle Pardossi-Piquard
Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique, UMR6097 CNRS UNSA, Valbonne 06560, France
Neuron 46:541-54. 2005..The presenilin-dependent regulation of neprilysin, mediated by AICDs, provides a physiological means to modulate Abeta levels with varying levels of gamma-secretase activity... - Regulation of cholesterol and sphingomyelin metabolism by amyloid-beta and presenilinMarcus O W Grimm
Centre for Molecular Biology Heidelberg, INF 282, D-69120 Heidelberg, Germany
Nat Cell Biol 7:1118-23. 2005..Our results demonstrate a biological function for APP processing and also a functional basis for the link that has been observed between lipids and Alzheimer's disease (AD)... - Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcineQi Zhang
Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
Cardiovasc Diabetol 6:16. 2007..The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process... - A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor poolMarta G del Barrio
Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
Development 134:3427-36. 2007.... - Defective signal transduction in B lymphocytes lacking presenilin proteinsTomohito Yagi
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 105:979-84. 2008..Our findings also suggest that pharmacologic inhibition of PS for the treatment of conditions such as Alzheimer's disease may have potential consequences for immune system function... - Resistance to drug by different isolates Trypanosoma evansi in ChinaJinlin Zhou
Shanghai Institute of Animal Parasitology, Chinese Academy of Agricultural Sciences, 3 Lane 345, Shilong Road, Shanghai 200232, China
Acta Trop 90:271-5. 2004..No drug cross-resistance was observed between suramin and antrycide...
Research Grants
- PINK1 and Recessive ParkinsonismJie Shen; Fiscal Year: 2007..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of Parkingson's disease and to characterize the molecular pathways responsible for PD pathogenesis. ..
- DJ-1 in Dopaminergic Neuronal Function and SurvivalJie Shen; Fiscal Year: 2007..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of PD and to characterize the molecular pathways responsible for PD pathogenesis. ..
- PINK1 and Recessive ParkinsonismJie Shen; Fiscal Year: 2009..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of Parkingson's disease and to characterize the molecular pathways responsible for PD pathogenesis. ..
- DJ-1 in Dopaminergic Neuronal Function and SurvivalJie Shen; Fiscal Year: 2009..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of PD and to characterize the molecular pathways responsible for PD pathogenesis. ..
- Presenilins in Synaptic Plasticity and NeurodegenerationJie Shen; Fiscal Year: 2010..Furthermore, identification of the molecular pathways regulated by PS may provide novel therapeutic targets for combating cognitive dysfunction and neurodegeneration in these disorders. ..
- PINK1 and Recessive ParkinsonismJie Shen; Fiscal Year: 2009..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of PD and to characterize the molecular pathways responsible for PD pathogenesis. ..
- Presenilins, Gamma-Secretase and Notch in Neuronal DeathJie Shen; Fiscal Year: 2010..Better understanding of the molecular pathways by which presenilins regulate cognitive and neuronal integrity will provide important insights into the pathogenesis of these disorders and may provide novel therapeutic targets. ..
- Function and Dysfunction of LRRK2Jie Shen; Fiscal Year: 2010..Completion of our proposed study will provide insights into PD pathogenesis and may identify novel therapeutic targets for development of more effective drugs. ..
- PINK1 and Parkin in dopaminergic and mitochondrial functionsJie Shen; Fiscal Year: 2010..Completion of our proposed study will provide insights into PD pathogenesis and may identify novel therapeutic targets for development of more effective drugs. ..
- Presenilins in Synaptic Plasticity and NeurodegenerationJie Shen; Fiscal Year: 2007..Furthermore, identification of the molecular pathways regulated by PS may provide novel therapeutic targets for combating cognitive dysfunction and neurodegeneration in these disorders. ..
- PS-1 in APP Processing and Synaptic FunctionJie Shen; Fiscal Year: 2004..The significance of the proposed study is that it will elucidate the normal physiological role of PS1 in the adult brain and test the feasibility and suitability of targeting PS1 for anti-amyloidogenic therapy in Alzheimer's disease. ..
- Studies of Parkin KO Cells and Mice as PD ModelsJie Shen; Fiscal Year: 2004..Both the animal and the cellular systems could provide valuable means for identifying and testing molecules and genes with therapeutic potential. ..
- PS1 & PS2 in Cortical Development and Notch SignalingJie Shen; Fiscal Year: 2006....
- PINK1 and Recessive ParkinsonismJie Shen; Fiscal Year: 2010..Our long-term goal is to develop a genetic mouse model that recapitulates all central features of Parkingson's disease and to characterize the molecular pathways responsible for PD pathogenesis. ..