Research Topics
Genomes and Genes
| Bart De StrooperSummaryAffiliation: Katholieke Universiteit Leuven Country: Belgium Publications
| Collaborators
|
Detail Information
Publications
Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer's disease-associated presenilinsB De Strooper
Experimental Genetics Group, Belgium
J Biol Chem 272:3590-8. 1997....- Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor proteinB De Strooper
Experimental Genetics Group, Flemish Institute for Biotechnology VIB4, Center for Human Genetics, K U Leuven, Belgium
Nature 391:387-90. 1998..Our results indicate that mutations in PS1 that manifest clinically cause a gain of function and that inhibition of PS1 activity is a potential target for anti-amyloidogenic therapy in Alzheimer's disease... - A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domainB De Strooper
Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology VIB4, Center for Human Genetics, KU Leuven, Belgium
Nature 398:518-22. 1999..Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling... - Amyloid-beta precursor protein processing in neurodegenerationValérie Wilquet
Laboratory for Neuronal Cell Biology and Gene Transfer, K U Leuven and VIB, Department of Human Genetics, Herestraat 49, 3000 Leuven, Belgium
Curr Opin Neurobiol 14:582-8. 2004..However, the absence of consistent and informative phenotypes in different loss of function animal models make elucidating the molecular actions of the amyloid-beta precursor protein an ongoing challenge... - Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complexBart De Strooper
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, K U Leuven and Flanders Interuniversitary Institute for Biotechnology, VIB4, Leuven, Belgium
Neuron 38:9-12. 2003..Gamma-Secretase is an interesting but complex drug target that challenges classical thinking about proteolytic processing and intracellular signaling... - Coordinated and widespread expression of gamma-secretase in vivo: evidence for size and molecular heterogeneitySébastien S Hébert
Neuronal Cell Biology and Gene Transfer, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology VIB4 and K U Leuven, 3000 Leuven, Belgium
Neurobiol Dis 17:260-72. 2004..In conclusion, our results suggest that gamma-secretase is a heterogeneous family of protein complexes widely expressed in the adult organism... 
The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivoLujia Zhou
VIB Center for the Biology of Disease, KULeuven, 3000 Leuven, Belgium
J Biol Chem 287:25927-40. 2012..This work provides molecular insights into the function and the pathways in which BACE1 is involved, and it will help to predict or interpret possible side effects of BACE1 inhibitor drugs in current clinical trials...
LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosisSamer Matta
VIB Center for the Biology of Disease, 3000 Leuven, Belgium
Neuron 75:1008-21. 2012....- Regulated intramembrane proteolysis of amyloid precursor protein and regulation of expression of putative target genesSébastien S Hébert
Neuronal Cell Biology and Gene Transfer, CME, Flanders Interuniversity Institute for Biotechnolog, VIB4, and Katholieke Universiteit Leuven, Herestraat 49, Leuven 3000, Belgium
EMBO Rep 7:739-45. 2006..Therefore, inhibition of APP processing to decrease Abeta generation in Alzheimer's disease will not interfere significantly with the function of these genes... - Presenilin clinical mutations can affect gamma-secretase activity by different mechanismsMostafa Bentahir
Neuronal Cell Biology and Gene Transfer, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB4) and K. U. Leuven, Leuven, Belgium
J Neurochem 96:732-42. 2006..Finally, subtle differences in gamma-secretase complex assembly were observed. Overall, our results indicate that the different mutations in PS affect gamma-secretase structure or function in multiple ways... - MicroRNA regulation of Alzheimer's Amyloid precursor protein expressionSébastien S Hébert
Center for Human Genetics, KULeuven, Belgium
Neurobiol Dis 33:422-8. 2009..This possibility is further corroborated by the observation that a statistically significant decrease in miR-106b expression was found in sporadic AD patients... - gamma-Secretase heterogeneity in the Aph1 subunit: relevance for Alzheimer's diseaseLutgarde Serneels
Department for Molecular and Developmental Genetics, VIB, KULeuven, Herestraat 49, 3000 Leuven, Belgium
Science 324:639-42. 2009..The Aph1B complex contributes to total gamma-secretase activity in the human brain, and thus specific targeting of Aph1B-containing gamma-secretase complexes may help generate less toxic therapies for Alzheimer's disease... - The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutantsSven Vilain
VIB Center for Biology of Disease, Katholieke Universiteit Leuven, Leuven, Belgium
PLoS Genet 8:e1002456. 2012.... - Alterations in phosphatidylethanolamine levels affect the generation of AβIva Nesic
Center for Human Genetics, Leuven Institute for Neurodegenerative Diseases, KU Leuven, Leuven, Belgium
Aging Cell 11:63-72. 2012..These results suggest that modulation of the membrane-soluble domains could be a valuable alternative to reduce excessive Aβ generation... - Peroxisome-proliferator-activated receptor gamma induces a clearance mechanism for the amyloid-beta peptideIra Espuny Camacho
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, Vlaams Interuniversitair Instituut voor Biotechnologie and Katholieke Universiteit Leuven, 3000 Leuven, Belgium
J Neurosci 24:10908-17. 2004..Our results suggest that PPARgamma-controlled mechanisms should be explored further as potential drug targets for Alzheimer's disease treatment... - Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type PresenilinOmar Nyabi
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology VIB4 and K U Leuven, 3000 Leuven, Belgium
J Biol Chem 278:43430-6. 2003.... - Phenotypic and biochemical analyses of BACE1- and BACE2-deficient miceDiana Dominguez
Center for Human Genetics, Katholieke Universiteit Leuven and Flanders Interuniversity Institute for Biotechnology VIB4, Herestraat 49, 3000 Leuven, Belgium
J Biol Chem 280:30797-806. 2005..In conclusion, our data challenge the general idea of BACE1 as a safe drug target and call for some caution when claiming that no major side effects should be expected from blocking BACE1 activity... - The mechanism of γ-Secretase dysfunction in familial Alzheimer diseaseLucia Chávez-Gutiérrez
VIB Center for the Biology of Disease, Leuven, Belgium
EMBO J 31:2261-74. 2012.... - Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-β production by altering Nicastrin maturation and intracellular localizationVasiliki Michaki
Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases, KU Leuven, 3000 Leuven, Belgium
J Biol Chem 287:1100-11. 2012..Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered γ-secretase processing of APP, and thus Aβ generation, without affecting Notch cleavage... - Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expressionSébastien S Hébert
Center for Human Genetics, Katholieke Universiteit Leuven and Department of Molecular and Developmental Genetics, VIB, Herestraat 49 bus 602, B 3000 Leuven, Belgium
Proc Natl Acad Sci U S A 105:6415-20. 2008..We propose that loss of specific miRNAs can contribute to increased BACE1 and Abeta levels in sporadic AD... - Glu(332) in the Nicastrin ectodomain is essential for gamma-secretase complex maturation but not for its activityLucia Chávez-Gutiérrez
Center for Human Genetics, KULeuven, and Department for Molecular and Developmental Genetics, VIB4, Herestraat 49, Leuven, Belgium
J Biol Chem 283:20096-105. 2008..Consequently, these studies indicate that the main role of the Glu(332) is in the maturation and assembly of gamma-secretase rather than in the recognition of the substrates... - ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1Ragna Sannerud
Laboratory of Membrane Trafficking, Center for Human Genetics, Catholic University of Leuven, Leuven, Belgium
Proc Natl Acad Sci U S A 108:E559-68. 2011..It thereby provides a novel avenue to interfere with Aβ production through a selective modulation of the distinct endosomal transport routes used by BACE1 or APP... - The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortexEllen Jorissen
Center for Human Genetics, Katholieke Universiteit Leuven, Vlaams Instituut voor Biotechnologie VIB, 3000 Leuven, Belgium
J Neurosci 30:4833-44. 2010..Our study reveals that ADAM10 plays a central role in the developing brain by controlling mainly Notch-dependent pathways but likely also by reducing surface shedding of other neuronal membrane proteins including APP... 
Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathwayCary Esselens
Membrane Trafficking Laboratory, CME VIB04, Gasthuisberg KU Leuven, 3000 Leuven, Belgium
J Cell Biol 166:1041-54. 2004..Collectively, PS1 deficiency affects in a gamma-secretase-independent fashion the turnover of TLN through autophagic vacuoles, most likely by an impaired capability to fuse with lysosomes...- Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiencyMelissa Vos
VIB Center for the Biology of Disease, Leuven, Belgium
Science 336:1306-10. 2012..Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production... - gamma-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylationAn Herreman
Laboratory for Neuronal Cell Biology, Center for Human Genetics, Gasthuisberg KULeuven and Flanders Interuniversity Institute for Biotechnology VIB, Herestraat 49, 3000 Leuven, Belgium
J Cell Sci 116:1127-36. 2003..Because the trafficking of nicastrin to the Golgi apparatus is dependent on presenilins, our data point to a central role of presenilin in nicastrin maturation/localization, which could help to partially resolve the 'spatial paradox'... - Neurons generated from APP/APLP1/APLP2 triple knockout embryonic stem cells behave normally in vitro and in vivo: lack of evidence for a cell autonomous role of the amyloid precursor protein in neuronal differentiationBruno A Bergmans
Laboratory of Neuronal Cell Biology and Gene Transfer, Leuven, Belgium
Stem Cells 28:399-406. 2010..Our stem cell culture provides an excellent tool to circumvent the problem of lack of viability of APP/APLP triple knockout mice and will help to explore the function of this intriguing protein further in vitro and in vivo... - Presenilin-1 maintains a nine-transmembrane topology throughout the secretory pathwayDragana Spasic
Laboratory of Membrane Trafficking, Department of Human Genetics, Gasthuisberg, Katholieke Universiteit Leuven VIB11, B 3000 Leuven, Belgium
J Biol Chem 281:26569-77. 2006..This topology is independently underscored by lysine mutagenesis, cell surface biotinylation, and cysteine derivation strategies and is compatible with the different physiological functions assigned to presenilin-1... - Peroxisome proliferator-activated receptor gamma enhances the activity of an insulin degrading enzyme-like metalloprotease for amyloid-beta clearanceIra Espuny-Camacho
Center for Human Genetics, KU Leuven, Leuven, Belgium
J Alzheimers Dis 20:1119-32. 2010..We conclude that PPARgamma activates an IDE-like Abeta degrading activity. Our work suggests a drugable pathway that can clear Abeta peptide from the brain... - Contribution of presenilin transmembrane domains 6 and 7 to a water-containing cavity in the gamma-secretase complexAlexandra Tolia
Neuronal Cell Biology and Gene Transfer Laboratory, Center for Human Genetics, VIB4 and K U Leuven, Herestraat 49, 3000 Leuven, Belgium
J Biol Chem 281:27633-42. 2006..Our data suggest the possibility that more selective gamma-secretase inhibitors could be designed... - The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neuronsAmantha Thathiah
Department of Molecular and Developmental Genetics, Vlaams Institute for Biotechnology, Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium
Science 323:946-51. 2009..Thus, GPR3 represents a potential therapeutic target for the treatment of Alzheimer's disease... - ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretaseThomas Tousseyn
Center for Human Genetics, Katholieke Universiteit Leuven K U Leuven, Department for Developmental and Molecular Genetics, and Laboratory of Membrane Trafficking, Vlaams Instituut voor Biotechnologie VIB, K U Leuven, B 3000 Leuven, Belgium
J Biol Chem 284:11738-47. 2009..Thus, ADAM10 performs a dual role in cells, as a metalloprotease when it is membrane-bound, and as a potential signaling protein once cleaved by ADAM9/15 and the gamma-Secretase... - Peptides based on the presenilin-APP binding domain inhibit APP processing and Aβ production through interfering with the APP transmembrane domainCary Esselens
Laboratory for Membrane Trafficking, Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
FASEB J 26:3765-78. 2012..In cell-based assays, the peptide strongly suppressed APP shedding, demonstrating that it exerts the inhibitory effect already upstream of γ-secretase, most likely through steric hindrance... - Molecular biology. miRNAs in neurodegenerationSébastien S Hébert
Center for Human Genetics, VIB and KULeuven, Herestraat 49, Leuven, Belgium
Science 317:1179-80. 2007 - A novel strategy for the comprehensive analysis of the biomolecular composition of isolated plasma membranesDeepak B Thimiri Govinda Raj
Department of Molecular and Developmental Genetics VIB11, Laboratory for Membrane Trafficking and Center for Human Genetics KULeuven, Gasthuisberg O and N4, Leuven, Belgium
Mol Syst Biol 7:541. 2011..Since PM proteins provide many pathologically relevant biomarkers representing two-thirds of the currently used drug targets, this novel technology has great potential for biomedical and pharmaceutical applications... - Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomainsTomoko Wakabayashi
Center for Human Genetics, K U Leuven, Herestraat 49, B 3000 Leuven, Belgium
Nat Cell Biol 11:1340-6. 2009..Thus, these studies suggest that maintenance of the integrity of tetraspanin microdomains contributes to the refinement of proteolytic activity of the gamma-secretase complex... - Inhibition of beta-secretase in vivo via antibody binding to unique loops (D and F) of BACE1Lujia Zhou
Department of Molecular and Developmental Genetics, VIB, 3000 Leuven, Belgium
J Biol Chem 286:8677-87. 2011.... - Modification of γ-secretase by nitrosative stress links neuronal ageing to sporadic Alzheimer's diseaseFrancesc X Guix
VIB Center for Biology of Disease VIB, Leuven, Belgium
EMBO Mol Med 4:660-73. 2012..Furthermore, we found that peroxynitrite shifted the production of Aβ towards Aβ(42) and increased the Aβ(42) /Aβ(40) ratio. Our work identifies nitrosative stress as a potential mechanistic link between ageing and AD... - Synaptic dysfunction in hippocampus of transgenic mouse models of Alzheimer's disease: a multi-electrode array studySeon Ah Chong
Bio Electronic Systems, IMEC, Kapeldreef 75, Leuven, Belgium
Neurobiol Dis 44:284-91. 2011..V717I mice and depressed in biAT mice. The findings demonstrate important synaptic changes that differ considerably in the hippocampal sub-regions already at young age, well before the typical amyloid or tau pathology is evident... - Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brainMaarten Leyssen
Laboratory of Neurogenetics, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology VIB and University of Leuven, School of Medicine, Leuven, Belgium
EMBO J 24:2944-55. 2005..Finally, we also found interactions between APP and the JNK stress kinase cascade. Our findings suggest a role for APP in axonal outgrowth after traumatic brain injury... - BACE1 and presenilin: two unusual aspartyl proteases involved in Alzheimer's diseaseDiana Ines Dominguez
Neuronal Cell Biology and Gene Transfer Laboratory, Department of Human Genetics, KU Leuven and VIB4, Leuven, Belgium
Neurodegener Dis 1:168-74. 2004.... - Syndecan 3 intramembrane proteolysis is presenilin/gamma-secretase-dependent and modulates cytosolic signalingJoachim G Schulz
Glycobiology and Developmental Genetics, University of Leuven, Leuven, Belgium
J Biol Chem 278:48651-7. 2003..The cleavage is mediated by presenilin/gamma-secretase complex and negatively regulates the plasma membrane targeting of the transcriptional cofactor CASK... - Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic functionVanessa A Morais
Center for Human Genetics, K U Leuven, Leuven, Belgium
EMBO Mol Med 1:99-111. 2009..As Complex I dysfunction is also implicated in sporadic PD, a convergence of genetic and environmental causes of PD on a similar mitochondrial molecular mechanism appears to emerge... - G protein-coupled receptors, cholinergic dysfunction, and Abeta toxicity in Alzheimer's diseaseAmantha Thathiah
Molecular and Developmental Genetics, VIB, Leuven, Belgium
Sci Signal 2:re8. 2009.... - Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer diseaseBart De Strooper
KULeuven and Flanders Interuniversitary Institute for Biotechnology VIB, Centre for Human Genetics, Herestraat 49, 3000 Leuven, Belgium
EMBO Rep 8:141-6. 2007..In this review, I evaluate the implications of this model for the amyloid-cascade hypothesis and for the efficacy of presenilin/gamma-secretase as a drug target... - Presenilins in memory, Alzheimer's disease, and therapyEls Marjaux
Laboratory for Neuronal Cell Biology and Gene Transfer, Center for Human Genetics, VIB4, K.U.Leuven, UZ Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
Neuron 42:189-92. 2004..The question arises as to what extent these observations should influence our thinking on the pathogenesis of Alzheimer's disease and on strategies to further develop gamma-secretase inhibitors... - β-arrestin 2 regulates Aβ generation and γ-secretase activity in Alzheimer's diseaseAmantha Thathiah
1 Vlaams Instituut voor Biotechnologie VIB Center for the Biology of Disease, Leuven, Belgium 2 Center for Human Genetics and Leuven Institute for Neuroscience and Disease LIND, University of Leuven KU Leuven, Leuven, Belgium
Nat Med 19:43-9. 2013..Collectively, these studies identify β-arrestin 2 as a new therapeutic target for reducing amyloid pathology and GPCR dysfunction in Alzheimer's disease... - The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptorAikaterini S Papadopoulou
VIB, Leuven, Belgium
Nat Immunol 13:181-7. 2012..In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity... - The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothesIryna Benilova
Center for Human Genetics and Leuven Institute for Neurodegenerative diseases LIND, University of Leuven, Leuven, Belgium
Nat Neurosci 15:349-57. 2012..Here we critically review the evidence supporting toxic Aβ oligomers as drivers of neurodegeneration and make some suggestions that might facilitate progress in this complex field... - Amyloid precursor protein mutation E682K at the alternative β-secretase cleavage β'-site increases Aβ generationLujia Zhou
Department for Developmental and Molecular Genetics, VIB, Leuven, Belgium
EMBO Mol Med 3:291-302. 2011..We propose to classify the E682K mutation as probable pathogenic awaiting further independent confirmation of its association with AD in other patients... - Functional and topological analysis of Pen-2, the fourth subunit of the gamma-secretase complexLeen Bammens
Laboratory for the Research of Neurodegenerative Diseases, Center for Human Genetics, KULeuven, Leuven, Belgium
J Biol Chem 286:12271-82. 2011..Our study supports the hypothesis that Pen-2 is more than a structural component of the γ-secretase complex and may contribute to the catalytic mechanism of the enzyme... - The amyloid-beta precursor protein: integrating structure with biological functionConstanze Reinhard
Laboratory for Neuronal Cell Biology and Gene Transfer, Department of Human Genetics, Center for Human Genetics, KU Leuven and VIB, Leuven, Belgium
EMBO J 24:3996-4006. 2005..The biological function of APP itself remains, however, unclear. In the current review, we study in detail the different subdomains of APP and try to assign functional significance to particular structures identified in the protein... - Neurotoxicity of Alzheimer's disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratioInna Kuperstein
Department for Molecular and Developmental Genetics, Flanders Institute for Biotechnology VIB, Leuven, Belgium
EMBO J 29:3408-20. 2010..Our work also suggests the dynamic nature of the equilibrium between toxic and non-toxic intermediates... - Nicastrin: gatekeeper of the gamma-secretase complexBart De Strooper
Center for Human Genetics, VIB4 and KULeuven, 3000 Leuven, Belgium
Cell 122:318-20. 2005..2005) reveal the function of nicastrin, the largest member of the gamma-secretase complex. They show that the nicastrin extracellular domain is essential for recognition of substrate by the gamma-secretase... - The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblastsDieter Hartmann
Center for Human Genetics KU Leuven and Flanders Interuniversity Institute for Biotechnology, VIB 4 KU Leuven, VIB 7 Celgen, Herestraat 49, 3000 Leuven, Belgium
Hum Mol Genet 11:2615-24. 2002..Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity... - Comparison and meta-analysis of microarray data: from the bench to the computer deskYves Moreau
Department of Electrical Engineering ESAT SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, 3001, Heverlee Leuven, Belgium
Trends Genet 19:570-7. 2003.... - Tumour necrosis factor-alpha, interleukin-6 and interleukin-8 do not promote adhesion of human endometrial epithelial cells to mesothelial cells in a quantitative in vitro modelSophie Debrock
Leuven University Fertility Center, UZ Gasthuisberg, KU Leuven, Belgium
Hum Reprod 21:605-9. 2006..Using the QIVA, the hypothesis was tested that tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8) promote adhesion of endometrial epithelial cells to mesothelial cells... - Alterations of the microRNA network cause neurodegenerative diseaseSébastien S Hébert
Center for Human Genetics, K U Leuven, Herestraat 49 bus 602, B 3000 Leuven, Belgium
Trends Neurosci 32:199-206. 2009..Thus, miRNAs are moving rapidly center stage as key regulators of neuronal development and function in addition to important contributors to neurodegenerative disorder... - Gene profiling of hippocampal neuronal cultureMichal Dabrowski
Laboratory for Neuronal Cell Biology, Center for Human Genetics, and Department of Electrical Engineering ESAT-SCD, Katholieke Universiteit Leuven and VIB (Flemish Interuniversity Institute for Biotechnology, Leuven, Belgium
J Neurochem 85:1279-88. 2003..Our results also demonstrate that a comparison across the two experimental platforms (cDNA microarrays and oligonucleotide chips) and across different biological paradigms is feasible... - Proteases and proteolysis in Alzheimer disease: a multifactorial view on the disease processBart De Strooper
Center for Human Genetics, K U Leuven and Department for Molecular and Developmental Genetics, VIB, Leuven, Belgium
Physiol Rev 90:465-94. 2010..Blocking or stimulating these pathways provide, or have the potential to provide, interesting drug targets, which raises the hope that we will be able to provide a cure for this dreadful disorder... - Mitochondria dysfunction and neurodegenerative disorders: cause or consequenceVanessa A Morais
Center for Human Genetics, K U Leuven, Belgium
J Alzheimers Dis 20:S255-63. 2010..For Alzheimer's disease, the evidence in favor of such a link is more indirect, and mitochondrial dysfunction likely occurs at a later stage of the disorder... - gamma-secretases: from cell biology to therapeutic strategiesBruno A Bergmans
Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
Lancet Neurol 9:215-26. 2010.... - Novel research horizons for presenilins and γ-secretases in cell biology and diseaseBart De Strooper
Center for Human Genetics, Katholieke Universiteit Leuven, and Department for Molecular and Developmental Genetics, VIB, Leuven, Belgium
Annu Rev Cell Dev Biol 26:235-60. 2010..This novel knowledge will help to develop better drugs for Alzheimer's disease and cancer. We critically evaluate literature that proposes presenilin functions outside of the γ-secretase complex... - The secretases: enzymes with therapeutic potential in Alzheimer diseaseBart De Strooper
Center for Human Genetics, VIB and KULeuven, Herestraat 49, Leuven, Belgium
Nat Rev Neurol 6:99-107. 2010..Success or failure of these first-generation AD therapies will have enormous consequences for further drug development efforts for AD and possibly other neurodegenerative conditions... - Gamma-secretase and the intramembrane proteolysis of NotchEllen Jorissen
Center for Human Genetics, KULeuven, Leuven, Belgium
Curr Top Dev Biol 92:201-30. 2010..Finally we explore the recent insight that there are several gamma-secretase complexes in mammalian and discuss possibilities to use gamma-secretase as a drug target in Alzheimer's disease and cancer... - Prion protein in Alzheimer's pathogenesis: a hot and controversial issueIryna Benilova
Department for Molecular and Developmental Genetics, Flanders Institute for Biotechnology VIB, Leuven, Belgium
EMBO Mol Med 2:289-90. 2010.... - A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseasesWim Mandemakers
Center for Human Genetics, K U Leuven, Department of Molecular and Developmental Genetics, VIB, Herestraat 49, 3000 Leuven, Belgium
J Cell Sci 120:1707-16. 2007..The emerging evidence clearly demonstrates the crucial role of specific mitochondrial functions in maintaining neuronal circuit integrity... - The role of G protein-coupled receptors in the pathology of Alzheimer's diseaseAmantha Thathiah
Department for Molecular and Developmental Genetics, Flanders Institute for Biotechnology VIB, Leuven, Belgium
Nat Rev Neurosci 12:73-87. 2011..Additionally, amyloid-β has been shown to perturb GPCR function. Emerging insights into the mechanistic link between GPCRs and AD highlight the potential of this class of receptors as a therapeutic target for AD... - Structure and function of gamma-secretaseAlexandra Tolia
Center for Human Genetics, KULeuven and Department for Developmental and Molecular Genetics, VIB, Herestraat 49, 3000 Leuven, Belgium
Semin Cell Dev Biol 20:211-8. 2009..Here we review current knowledge about the structure and function of gamma-secretase and discuss the value of these findings for the mechanistic understanding of this unusual protease... - Non-coding RNAs with essential roles in neurodegenerative disordersEvgenia Salta
Centre for Human Genetics and Leuven Institute for Neurodegenerative Disorders LIND, University of Leuven, Leuven, Belgium
Lancet Neurol 11:189-200. 2012..This emerging field is anticipated to profoundly affect clinical research, diagnosis, and therapy in neurology... - Novel therapeutic strategies provide the real test for the amyloid hypothesis of Alzheimer's diseaseDiana Ines Dominguez
Centre for Human Genetics, VIB4 and K.U. Leuven, Herestraat 49, 3000 Leuven, Belgium
Trends Pharmacol Sci 23:324-30. 2002..Now, the major question is whether these drugs will work in the clinic... - Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synucleinErwin Lauwers
Gene Therapy Program, Katholieke Universiteit Leuven, Leuven, Belgium
Brain Pathol 13:364-72. 2003..Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases...