Konstanze F Winklhofer

Summary

Affiliation: University of Munich
Country: Germany

Publications

  1. ncbi request reprint Pathogenic mutations inactivate parkin by distinct mechanisms
    Iris H Henn
    Department of Cellular Biochemistry, Max Planck Institute for Biochemistry, Martinsried, Germany
    J Neurochem 92:114-22. 2005
  2. pmc Parkin is protective against proteotoxic stress in a transgenic zebrafish model
    Mareike E Fett
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    PLoS ONE 5:e11783. 2010
  3. doi request reprint Mitochondrial dysfunction in Parkinson's disease
    Konstanze 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
  4. pmc The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases
    Konstanze F Winklhofer
    Neurobiochemisty, Department of Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    EMBO J 27:336-49. 2008
  5. ncbi request reprint The parkin protein as a therapeutic target in Parkinson's disease
    Konstanze F Winklhofer
    Ludwig Maximilians University, Adolf Butenandt Institute, Department of Biochemistry, Schillerstrasse 44, 80336 Munich, Germany
    Expert Opin Ther Targets 11:1543-52. 2007
  6. doi request reprint Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation
    Julia 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
  7. pmc Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation
    A 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
  8. pmc The α-helical structure of prodomains promotes translocation of intrinsically disordered neuropeptide hormones into the endoplasmic reticulum
    Daniela Dirndorfer
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, 80336 Munich, Germany
    J Biol Chem 288:13961-73. 2013
  9. pmc alpha-Helical domains promote translocation of intrinsically disordered polypeptides into the endoplasmic reticulum
    Margit Miesbauer
    Neurobiochemistry, Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institut, Ludwig Maximilians Universitat Munchen, D 80336 MUnchen, Germany
    J Biol Chem 284:24384-93. 2009
  10. ncbi request reprint Targeting of the prion protein to the cytosol: mechanisms and consequences
    Margit 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

Collaborators

Detail Information

Publications37

  1. ncbi request reprint Pathogenic mutations inactivate parkin by distinct mechanisms
    Iris 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...
  2. pmc Parkin is protective against proteotoxic stress in a transgenic zebrafish model
    Mareike 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...
  3. doi request reprint Mitochondrial dysfunction in Parkinson's disease
    Konstanze 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...
  4. pmc The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases
    Konstanze 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...
  5. ncbi request reprint The parkin protein as a therapeutic target in Parkinson's disease
    Konstanze 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...
  6. doi request reprint Aberrant folding of pathogenic Parkin mutants: aggregation versus degradation
    Julia 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
    ....
  7. pmc Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation
    A 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...
  8. pmc The α-helical structure of prodomains promotes translocation of intrinsically disordered neuropeptide hormones into the endoplasmic reticulum
    Daniela Dirndorfer
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, 80336 Munich, Germany
    J Biol Chem 288:13961-73. 2013
    ..Our study reveals a novel function of prodomains to enable import of small or intrinsically disordered secretory proteins into the ER based on their ability to adopt an α-helical conformation...
  9. pmc alpha-Helical domains promote translocation of intrinsically disordered polypeptides into the endoplasmic reticulum
    Margit Miesbauer
    Neurobiochemistry, Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institut, Ludwig Maximilians Universitat Munchen, D 80336 MUnchen, Germany
    J Biol Chem 284:24384-93. 2009
    ..Our study indicates that extended unstructured domains are signals to dispose ER-targeted proteins via a co-translocational, preemptive quality control pathway...
  10. ncbi request reprint Targeting of the prion protein to the cytosol: mechanisms and consequences
    Margit 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
    ....
  11. pmc Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria
    Natalie 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...
  12. doi request reprint Neuroprotective and neurotoxic signaling by the prion protein
    Ulrike 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...
  13. pmc Stress-protective signalling of prion protein is corrupted by scrapie prions
    Angelika 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...
  14. pmc The heat shock response is modulated by and interferes with toxic effects of scrapie prion protein and amyloid β
    Ulrike 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...
  15. doi request reprint Parkin, PINK1 and mitochondrial integrity: emerging concepts of mitochondrial dysfunction in Parkinson's disease
    Anna 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...
  16. pmc Inhibition of mitochondrial fusion by α-synuclein is rescued by PINK1, Parkin and DJ-1
    Frits 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...
  17. pmc The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication
    Ulrike 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...
  18. doi request reprint The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO
    Anne Kathrin Müller-Rischart
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    Mol Cell 49:908-21. 2013
    ....
  19. pmc Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences
    Nicole 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...
  20. doi request reprint Green tea extracts interfere with the stress-protective activity of PrP and the formation of PrP
    Angelika 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)...
  21. pmc Association of Bcl-2 with misfolded prion protein is linked to the toxic potential of cytosolic PrP
    Angelika 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...
  22. ncbi request reprint Loss-of-function of human PINK1 results in mitochondrial pathology and can be rescued by parkin
    Nicole 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...
  23. doi request reprint Cellular prion protein mediates toxic signaling of amyloid beta
    Ulrike K Resenberger
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University Munich, Munich, Germany
    Neurodegener Dis 10:298-300. 2012
    ....
  24. pmc Conserved stress-protective activity between prion protein and Shadoo
    Vignesh 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...
  25. ncbi request reprint A pathogenic PrP mutation and doppel interfere with polarized sorting of the prion protein
    Armgard 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...
  26. ncbi request reprint Parkin mediates neuroprotection through activation of IkappaB kinase/nuclear factor-kappaB signaling
    Iris 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...
  27. ncbi request reprint Post-translational import of the prion protein into the endoplasmic reticulum interferes with cell viability: a critical role for the putative transmembrane domain
    Ulrich 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...
  28. pmc Systematic identification of antiprion drugs by high-throughput screening based on scanning for intensely fluorescent targets
    Uwe Bertsch
    Zentrum für Neuropathologie und Prionforschung, Ludwig Maximilians Universitat, Feodor Lynen Str 23, D 81377 Munchen, Germany
    J Virol 79:7785-91. 2005
    ..Moreover, SIFT-based screening may facilitate the search for drugs against other diseases linked to protein aggregation...
  29. pmc Structural instability of the prion protein upon M205S/R mutations revealed by molecular dynamics simulations
    Thomas Hirschberger
    Theoretische Biophysik, Lehrstuhl fur BioMolekulare Optik, Ludwig Maximilians Universitat, 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...
  30. ncbi request reprint [Inactivation of parkin in Parkinson disease]
    Konstanze F Winklhofer
    Pharm Unserer Zeit 35:186-7. 2006
  31. ncbi request reprint Pathogenic mutations located in the hydrophobic core of the prion protein interfere with folding and attachment of the glycosylphosphatidylinositol anchor
    Sophia 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...
  32. doi request reprint Observing fibrillar assemblies on scrapie-infected cells
    Susanne 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...
  33. ncbi request reprint Folding and misfolding of the prion protein in the secretory pathway
    Jorg 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...
  34. ncbi request reprint Misfolding of the prion protein at the plasma membrane induces endocytosis, intracellular retention and degradation
    Sophia Kiachopoulos
    Department of Cellular Biochemistry, Max Planck Institut fur Biochemie, 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...
  35. ncbi request reprint Inactivation of parkin by oxidative stress and C-terminal truncations: a protective role of molecular chaperones
    Konstanze 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...
  36. pmc Cofactor Tpr2 combines two TPR domains and a J domain to regulate the Hsp70/Hsp90 chaperone system
    Alexander 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...
  37. ncbi request reprint Determinants of the in vivo folding of the prion protein. A bipartite function of helix 1 in folding and aggregation
    Konstanze 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...