Research Topics
Genomes and Genes
| Konstanze F WinklhoferSummaryAffiliation: University of Munich Country: Germany Publications
| Collaborators
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Detail Information
Publications
Pathogenic mutations inactivate parkin by distinct mechanismsIris H Henn
Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, Martinsried, Germany
J Neurochem 92:114-22. 2005..Furthermore, we present evidence that a smaller parkin species of 42 kDa, which is present in extracts prepared from human brain and cultured cells, originates from an internal start site and lacks the N-terminal UBL domain...
The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseasesKonstanze F Winklhofer
Neurobiochemisty, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
EMBO J 27:336-49. 2008..Here, we summarize how these two faces of protein misfolding contribute to the pathomechanisms of Alzheimer's disease, frontotemporal lobar degeneration, Parkinson's disease and prion diseases...- The parkin protein as a therapeutic target in Parkinson's diseaseKonstanze F Winklhofer
Ludwig Maximilians University, Adolf Butenandt Institute, Department of Biochemistry, Schillerstrasse 44, 80336 Munich, Germany
Expert Opin Ther Targets 11:1543-52. 2007..This property makes parkin an attractive target for therapeutic strategies to prevent or halt the loss of dopaminergic neurons... 
Mitochondrial dysfunction in Parkinson's diseaseKonstanze F Winklhofer
German Center for Neurodegenerative Diseases DZNE Munich and Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Schillerstr 44, D 80336 Munich, Germany
Biochim Biophys Acta 1802:29-44. 2010..In fact, sporadic and familial PD seem to converge at the level of mitochondrial integrity...- Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentationA Kathrin Lutz
Neurobiochemistry, Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
J Biol Chem 284:22938-51. 2009..We propose that the discrepant findings in adult flies can be explained by the time of phenotype analysis and suggest that in mammals different strategies may have evolved to cope with dysfunctional mitochondria... - Parkin is protective against proteotoxic stress in a transgenic zebrafish modelMareike E Fett
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
PLoS ONE 5:e11783. 2010..In order to study the function of parkin in more detail and to address possible differences in its role in different species, we chose Danio rerio as a different vertebrate model system... - Neuroprotective and neurotoxic signaling by the prion proteinUlrike K Resenberger
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany
Top Curr Chem 305:101-19. 2011..In this review we will summarize current knowledge of neurotoxic PrP conformers and discuss the role of PrP(C) as a mediator of both stress-protective and neurotoxic signaling cascades... - Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson's diseaseAnna Pilsl
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
Acta Neuropathol 123:173-88. 2012..In this review we will summarize current knowledge about the impact of parkin and PINK1 on mitochondria... - The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replicationUlrike K Resenberger
Department of Metabolic Biochemistry, Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany
EMBO J 30:2057-70. 2011..Our study indicates that PrP(C) can mediate toxic signalling of various β-sheet-rich conformers independent of infectious prion propagation, suggesting a pathophysiological role of the prion protein beyond of prion diseases... - Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1Frits Kamp
DZNE German Center for Neurodegenerative Diseases, Adolf Butenandt Institute, Biochemistry, Ludwig Maximilians University, Munich, Germany
EMBO J 29:3571-89. 2010..Finally, mitochondrial fragmentation induced by expression of αS is rescued by coexpression of PINK1, parkin or DJ-1 but not the PD-associated mutations PINK1 G309D and parkin Δ1-79 or by DJ-1 C106A... - Targeting of the prion protein to the cytosol: mechanisms and consequencesMargit Miesbauer
German Center for Neurodegenerative Diseases DZNE, Munich and Adolf Butenandt Institute, Neurobiochemistry, Ludwig Maximilians University Munich, Schillerstrasse 44, D 80336 MUnchen, Germany
Curr Issues Mol Biol 12:109-18. 2010.... - The heat shock response is modulated by and interferes with toxic effects of scrapie prion protein and amyloid βUlrike K Resenberger
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, D 80336 Munich, Germany
J Biol Chem 287:43765-76. 2012..Our study supports the notion that different pathological protein conformers mediate toxic effects via similar cellular pathways and emphasizes the possibility to exploit the heat shock response therapeutically... - Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequencesNicole Exner
Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
EMBO J 31:3038-62. 2012..Studies on the function and dysfunction of these genes revealed that various aspects of mitochondrial biology appear to be affected in PD, comprising mitochondrial biogenesis, bioenergetics, dynamics, transport, and quality control... - Stress-protective signalling of prion protein is corrupted by scrapie prionsAngelika S Rambold
Department of Biochemistry, Neurobiochemistry, Ludwig Maximilians University Munich, Munchen, Germany
EMBO J 27:1974-84. 2008..Our results provide new insight into the mechanism of PrP(C)-mediated neuroprotection and indicate that pathological PrP conformers abuse PrP(C)-dependent pathways for apoptotic signalling... - Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrPAngelika S Rambold
Department of Biochemistry, Neurobiochemistry, Ludwig Maximilians Universitat Munchen, Munchen, Germany
J Neurochem 107:218-29. 2008..Our study emphasizes the important role of PrP(C) to protect cells from stress and indicate efficient intracellular pathways to degrade non-native conformations of PrP(C)... - Aberrant folding of pathogenic Parkin mutants: aggregation versus degradationJulia S Schlehe
Department of Biochemistry, Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Schillerstrasse 44, Munich D 80336, Germany
J Biol Chem 283:13771-9. 2008.... - Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrPAngelika S Rambold
Department of Biochemistry, Neurobiochemistry, Ludwig Maximilians Universitat Munchen, D 80336 MUnchen, Germany
Mol Biol Cell 17:3356-68. 2006..Our study reveals a compartment-specific toxicity of PrP misfolding that involves coaggregation of Bcl-2 and indicates a protective role of molecular chaperones... - Cellular prion protein mediates toxic signaling of amyloid betaUlrike K Resenberger
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany
Neurodegener Dis 10:298-300. 2012.... - Conserved stress-protective activity between prion protein and ShadooVignesh Sakthivelu
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, D 80336 Munich, Germany
J Biol Chem 286:8901-8. 2011..Our study reveals a conserved physiological activity between PrP(C) and Sho to protect cells from stress-induced toxicity and suggests that Sho and PrP(C) might act on similar signaling pathways... - Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkinNicole Exner
Center for Integrated Protein Science Munich and Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
J Neurosci 27:12413-8. 2007..Our results may therefore suggest that PINK1 deficiency in humans results in mitochondrial abnormalities associated with cellular stress, a pathological phenotype, which can be ameliorated by enhanced expression of parkin... - Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondriaNatalie V Pfeiffer
Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany
EMBO J 32:1036-51. 2013..In conclusion, our study reveals a novel mechanism of dual targeting to either the ER or mitochondria that is mediated by structural features within the nascent chain... - A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion proteinArmgard Uelhoff
Adolf Butenandt Institute, Department of Biochemistry, Laboratory for Alzheimer s and Parkinson s Disease Research, Ludwig Maximilians University, 80336 Munich, Germany
J Biol Chem 280:5137-40. 2005..Furthermore, a pathogenic PrP missense mutation within the HD leads to aberrant apical sorting of PrP as well... - Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signalingIris H Henn
Department of Biochemistry, Adolf Butenandt Institute, D 80336 Munich, Germany
J Neurosci 27:1868-78. 2007..Thus, our results support a direct link between the neuroprotective activity of parkin and ubiquitin signaling in the IKK/NF-kappaB pathway... - Structural instability of the prion protein upon M205S/R mutations revealed by molecular dynamics simulationsThomas Hirschberger
Theoretische Biophysik, , , Oettingenstrasse 67, D-80538 Munich, Germany
Biophys J 90:3908-18. 2006..Together with experimental evidence on model peptides, this decay suggests that the hydrophobic attachment of helix 1 to helix 3 at M205 is required for its correct folding into its stable native structure... - Post-translational import of the prion protein into the endoplasmic reticulum interferes with cell viability: a critical role for the putative transmembrane domainUlrich Heller
Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany
J Biol Chem 278:36139-47. 2003..Our study reveals that the putative transmembrane domain features in the formation of misfolded PrP conformers and indicates that post-translational targeting of PrP to the ER can decrease cell viability... - Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone systemAlexander Brychzy
Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18a, D 82152 Martinsried, Germany
EMBO J 22:3613-23. 2003..We propose a novel mechanism in which Tpr2 mediates the retrograde transfer of substrates from Hsp90 onto Hsp70. At normal levels substoichiometric to Hsp90 and Hsp70, this activity optimizes the function of the multichaperone machinery... - Inactivation of parkin by oxidative stress and C-terminal truncations: a protective role of molecular chaperonesKonstanze F Winklhofer
Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, D 82152 Martinsried, Germany
J Biol Chem 278:47199-208. 2003..Our study demonstrates that C-terminal truncations impede parkin folding and reveal a new mechanism for inactivation of parkin... - Misfolding of the prion protein at the plasma membrane induces endocytosis, intracellular retention and degradationSophia Kiachopoulos
Department of Cellular Biochemistry, , Am Klopferspitz 18, D-82152 Martinsried, Germany
Traffic 5:426-36. 2004..Our study revealed a quality control pathway for aberrant PrP conformers present at the plasma membrane and identified distinct PrP domains involved... - Folding and misfolding of the prion protein in the secretory pathwayJorg Tatzelt
Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, D 82152 Martinsried, Germany
Amyloid 11:162-72. 2004..All available data indicate that the only difference between PrPc and PrPSc resides in their conformation, emphasizing a critical role of protein folding in the pathogenesis of prion diseases... - Pathogenic mutations located in the hydrophobic core of the prion protein interfere with folding and attachment of the glycosylphosphatidylinositol anchorSophia Kiachopoulos
Department of Cellular Biochemistry, Max Planck Institute for Biochemie, D 82152 Martinsried, Germany
J Biol Chem 280:9320-9. 2005..Our study reveals that formation of the C-terminal globular domain of PrPC has an impact on membrane anchoring and indicates that misfolded secreted forms of the prion protein are linked to inherited prion diseases in humans... - Observing fibrillar assemblies on scrapie-infected cellsSusanne Wegmann
Center of Biotechnology, University of Technology, Dresden, Germany
Pflugers Arch 456:83-93. 2008..These endogeneous fibrils had lengths from 0.5 to 3 microm and protruded from the cell surface by 108 +/- 30 nm, and thus resembled the heterogeneous shapes and networks of in vitro prepared amyloid fibrils... - [Inactivation of parkin in Parkinson disease]Konstanze F Winklhofer
Pharm Unserer Zeit 35:186-7. 2006 - Systematic identification of antiprion drugs by high-throughput screening based on scanning for intensely fluorescent targetsUwe Bertsch
, , Feodor Lynen Str. 23, , Germany
J Virol 79:7785-91. 2005..Moreover, SIFT-based screening may facilitate the search for drugs against other diseases linked to protein aggregation... - Determinants of the in vivo folding of the prion protein. A bipartite function of helix 1 in folding and aggregationKonstanze F Winklhofer
Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, Am Klopferspitz 18a, D 82152 Martinsried, Germany
J Biol Chem 278:14961-70. 2003..Our study indicates a bipartite function of helix 1 in the maturation and aggregation of PrP and emphasizes a critical role of a membrane anchor in the formation of complex glycosylated PrP...