Research Topics
| G ThinakaranSummaryAffiliation: University of Chicago Country: USA Publications
Research Grants
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Detail Information
Publications
Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranesKulandaivelu S Vetrivel
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Illinois 60637, USA
J Biol Chem 279:44945-54. 2004..These findings are consistent with the localization of gamma-secretase in lipid raft microdomains of post-Golgi and endosomes, organelles previously implicated in amyloidogenic processing of APP...
Metabolism of presenilinsG Thinakaran
Department of Neurobiology, Pharmacology and Physiology, Center for Molecular Neurobiology, The University of Chicago, IL 60637, USA
J Mol Neurosci 17:183-92. 2001..Here I have reviewed the vast literature on the biology of PS, especially focusing on PS endoproteolysis and the accumulation of stable PS derivatives that are likely the functional units...- Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in micePing Gong
Departments of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, IL 60637, USA
Mol Neurodegener 6:87. 2011..Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden... - Identification of the role of presenilins beyond Alzheimer's diseaseGopal Thinakaran
Departments of Neurobiology, Pharmacology and Physiology, University of Chicago, Knapp R212, 924 East 57th Street, Chicago, IL 60637, USA
Pharmacol Res 50:411-8. 2004..This review summarizes the diverse physiological functions that are regulated by PSs beyond APP metabolism... - Amyloid precursor protein trafficking, processing, and functionGopal Thinakaran
Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 283:29615-9. 2008..This minireview summarizes salient features of APP trafficking and amyloidogenic processing and discusses the putative biological functions of APP... - Spatial segregation of gamma-secretase and substrates in distinct membrane domainsKulandaivelu S Vetrivel
Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 280:25892-900. 2005.... - Alzheimer disease Abeta production in the absence of S-palmitoylation-dependent targeting of BACE1 to lipid raftsKulandaivelu S Vetrivel
Department of Neurobiology, Neurology, and Pathology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 284:3793-803. 2009..These results indicate that post-translational S-palmitoylation of BACE1 is not required for APP processing, and that BACE1 can efficiently cleave APP in both raft and non-raft microdomains... - Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartmentsKulandaivelu S Vetrivel
Department of Neurobiology, Pharmacology and Physiology, University of Chicago, Chicago, IL 60637, USA
Neurology 66:S69-73. 2006..Here, we review the salient features of Alzheimer disease amyloidogenesis, and discuss the current knowledge on APP trafficking and amyloidogenic processing of APP in intracellular membrane compartments and microdomains... - Multiple effects of aspartate mutant presenilin 1 on the processing and trafficking of amyloid precursor proteinS H Kim
Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 276:43343-50. 2001..These findings lead us to conclude that the stability and trafficking of APP can be profoundly modulated by coexpression of PS1 with mutations at aspartate 257 and aspartate 385... - A role for presenilin 1 in regulating the delivery of amyloid precursor protein to the cell surfaceJae Yoon Leem
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Illinois 60637, USA
Neurobiol Dis 11:64-82. 2002..Collectively, our findings provide evidence that PS1 regulates the glycosylation and intracellular trafficking of APP and select membrane proteins... - Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementiaS H Kim
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Abbott 316, 947 East 58th Street, Chicago, Illinois 60637, USA
Nat Neurosci 2:984-8. 1999..Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates fibrillogenic peptides that initiate the pathogenesis of FBD... - Presenilin 1 is required for maturation and cell surface accumulation of nicastrinJae Yoon Leem
Department of Neurobiology, Committee on Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 277:19236-40. 2002..Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex... - Presenilin attenuates receptor-mediated signaling and synaptic functionAngèle T Parent
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, USA
J Neurosci 25:1540-9. 2005.... - Membrane rafts in Alzheimer's disease beta-amyloid productionKulandaivelu S Vetrivel
Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USA
Biochim Biophys Acta 1801:860-7. 2010..Then, we will discuss potential raft targeting signals identified in the secretases and their importance on amyloidogenic processing of APP... - S-palmitoylation of gamma-secretase subunits nicastrin and APH-1Haipeng Cheng
Department of Neurobiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 284:1373-84. 2009..Our findings suggest that S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate gamma-secretase processing of APP and other substrates... - Mechanisms of disease: new therapeutic strategies for Alzheimer's disease--targeting APP processing in lipid raftsHaipeng Cheng
University of Chicago, IL, USA
Nat Clin Pract Neurol 3:374-82. 2007.... - Investigation of unfolded-protein response in cells expressing familial Alzheimer's disease-linked presenilin variantsGopal Thinakaran
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, IL, USA
Methods Mol Biol 232:203-16. 2003 - Steady-state increase of cAMP-response element binding protein, Rac, and PAK signaling in presenilin-deficient neuronsNatalie Y Barnes
Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA
J Neurochem 104:1637-48. 2008..Our study highlights the importance of PS-dependent proteolytic cleavage of gamma-secretase substrates in regulating neuronal signal transduction... - Effects of PS1 deficiency on membrane protein trafficking in neuronsS Naruse
Department of Pharmacological and Physiological Sciences, The University of Chicago, Illinois 60637, USA
Neuron 21:1213-21. 1998..We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons... - Localization and regional distribution of p23/TMP21 in the brainKulandaivelu S Vetrivel
Department of Neurobiology, The University of Chicago, Chicago, IL 60637, USA
Neurobiol Dis 32:37-49. 2008..We conclude that p23 is expressed in neurons throughout the brain and the decline in p23 expression during postnatal development may significantly contribute to enhanced beta-amyloid production in the adult brain... - Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted AbetaKulandaivelu S Vetrivel
Department of Neurobiology and Neurology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 283:19489-98. 2008..In view of the known function of CD147 in MMP production, we postulate that CD147 expression influences Abeta levels by an indirect mechanism involving MMPs that can degrade extracellular Abeta... - Proteolytic processing of familial British dementia-associated BRI variants: evidence for enhanced intracellular accumulation of amyloidogenic peptidesSeong-Hun Kim
Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 277:1872-7. 2002..We propose that intracellular accumulation of amyloidogenic ADan or ABri peptides results in the neuronal damage leading to FDD and FBD, respectively... - Mutation analysis of the presenilin 1 N-terminal domain reveals a broad spectrum of gamma-secretase activity toward amyloid precursor protein and other substratesPing Gong
Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA
J Biol Chem 285:38042-52. 2010..We conclude that the N-terminal LL1 and TM2 domains are critical for PS1 endoproteolysis and the coordination between the putative substrate-docking site and the catalytic core of the γ-secretase... 
Psychosine accumulates in membrane microdomains in the brain of krabbe patients, disrupting the raft architectureAdam B White
Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA
J Neurosci 29:6068-77. 2009..This study provides a previously undescribed biophysical aspect for the mechanism of pathogenesis in Krabbe disease...- Stanniocalcin 2 is a negative modulator of store-operated calcium entryWilliam Zeiger
The University of Chicago, Chicago, Illinois 60637, USA
Mol Cell Biol 31:3710-22. 2011..Furthermore, our findings implicate the modulation of SOCE through STC2 expression as one of the prosurvival measures of the unfolded protein response... - Characterization of stanniocalcin 2, a novel target of the mammalian unfolded protein response with cytoprotective propertiesDaisuke Ito
Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Knapp R212, 924 East 57th St, Chicago, IL 60637, USA
Mol Cell Biol 24:9456-69. 2004..Consequently, induced STC2 expression is an essential feature of survival component of the UPR... - Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor proteinDongming Cai
Fisher Center for Research on Alzheimer s Disease and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 278:3446-54. 2003..These results suggest that PS1 regulation of beta APP trafficking may represent an alternative mechanism by which FAD-linked PS1 variants modulate beta APP processing... - Gamma-secretase is a functional component of phagosomesIsabelle Jutras
Departement de pathologie et biologie cellulaire, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada
J Biol Chem 280:36310-7. 2005..Finally, our results indicate that interferon-gamma stimulates gamma-secretase-dependent cleavages on phagosomes and that gamma-secretase activity may be involved in the phagocytic response of macrophages to inflammatory cytokines... - The role of presenilin cofactors in the gamma-secretase complexNobumasa Takasugi
Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyoku, Tokyo 113 0033, Japan
Nature 422:438-41. 2003..Thus, APH-1 stabilizes the presenilin holoprotein in the complex, whereas PEN-2 is required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex... - Presenilins and gamma-secretase inhibitors affect intracellular trafficking and cell surface localization of the gamma-secretase complex componentsHong Wang
The Fisher Center for Alzheimer's Disease Research and the Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 279:40560-6. 2004.... - Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase componentsYun Wu Zhang
Center for Neuroscience and Aging, The Burnham Institute, La Jolla, California 92037, USA
J Biol Chem 280:17020-6. 2005.... - PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1Wen Jie Luo
Fisher Center for Research on Alzheimer s Disease and Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York 10021, USA
J Biol Chem 278:7850-4. 2003..Our data reveal a direct role of PEN-2 in proteolytic cleavage of PS1 and a regulatory function of APH-1, in coordination with PEN-2, in the biogenesis of the PS1 complex... - Presenilins and Alzheimer disease: the calcium conspiracyGopal Thinakaran
Nat Neurosci 9:1354-5. 2006
Research Grants
- Mouse model for neuroprotectionGopal Thinakaran; Fiscal Year: 2007..Outcome of our investigation will be critical for the future development of STC2 based therapeutic strategy to prevent neuronal death. ..
- Amyloidogenic Processing of APPGopal Thinakaran; Fiscal Year: 2007....
- Cell Biology of Presenilin 1 and Associated ProteinsGopal Thinakaran; Fiscal Year: 2009..Our studies will be critical to develop novel rational AD therapeutics aimed at reducing beta-amyloid burden in the brain. ..
- Cell Biology of Presenilin 1 and Associated ProteinsGopal Thinakaran; Fiscal Year: 2010..Our studies will be critical to develop novel rational AD therapeutics aimed at reducing beta-amyloid burden in the brain. ..
- Amyloidogenic Processing of APPGopal Thinakaran; Fiscal Year: 2010....
- Cell Biology of Presenilin 1 and Associated ProteinsGopal Thinakaran; Fiscal Year: 2006..abstract_text> ..
- STRUCTURAL AND FUNCTIONAL ANALYSIS OF PRESENILINSGopal Thinakaran; Fiscal Year: 2005..Our efforts will focus on the role played by PS1 hydrophilic loop domain during mammalian embryonic development, and in the process of amyloid production/deposition in the brains of transgenic mice. ..
- Cell Biology of Presenilin 1 and Associated ProteinsGopal Thinakaran; Fiscal Year: 2009..Our studies will be critical to develop novel rational AD therapeutics aimed at reducing beta-amyloid burden in the brain. ..