M Goedert

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. ncbi request reprint Tau gene mutations and their effects
    Michel Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Mov Disord 20:S45-52. 2005
  2. ncbi request reprint Tau protein, the paired helical filament and Alzheimer's disease
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    J Alzheimers Dis 9:195-207. 2006
  3. pmc Detection of filamentous tau inclusions by the fluorescent Congo red derivative FSB [(trans,trans)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene]
    Ana Velasco
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    FEBS Lett 582:901-6. 2008
  4. doi request reprint 100 years of Lewy pathology
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nat Rev Neurol 9:13-24. 2013
  5. pmc Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
    Veronique Schaeffer
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Brain 135:2169-77. 2012
  6. pmc alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies
    M G Spillantini
    Medical Research Council Centre for Brain Repair and Department of Neurology, University of Cambridge, Robinson Way, Cambridge CB2 2PY, United Kingdom
    Proc Natl Acad Sci U S A 95:6469-73. 1998
  7. ncbi request reprint Parkinson's disease and other alpha-synucleinopathies
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Clin Chem Lab Med 39:308-12. 2001
  8. ncbi request reprint The significance of tau and alpha-synuclein inclusions in neurodegenerative diseases
    M Goedert
    MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK
    Curr Opin Genet Dev 11:343-51. 2001
  9. pmc From genetics to pathology: tau and alpha-synuclein assemblies in neurodegenerative diseases
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Philos Trans R Soc Lond B Biol Sci 356:213-27. 2001
  10. ncbi request reprint Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Their relevance for understanding the neurogenerative process
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Ann N Y Acad Sci 920:74-83. 2000

Collaborators

Detail Information

Publications94

  1. ncbi request reprint Tau gene mutations and their effects
    Michel Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Mov Disord 20:S45-52. 2005
    ..Moreover, the H1 haplotype of Tau has been identified as a significant risk factor for progressive supranuclear palsy and corticobasal degeneration...
  2. ncbi request reprint Tau protein, the paired helical filament and Alzheimer's disease
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    J Alzheimers Dis 9:195-207. 2006
    ..By the early 1990s, it was clear that tau protein is the major component of the paired helical filament and that the latter is made of all six tau isoforms, each full-length and hyperphosphorylated...
  3. pmc Detection of filamentous tau inclusions by the fluorescent Congo red derivative FSB [(trans,trans)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene]
    Ana Velasco
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    FEBS Lett 582:901-6. 2008
    ..More importantly, tau inclusions in the spinal cord of human P301S tau transgenic mice were labelled following a single intravenous injection of FSB. These findings indicate that FSB can be used to detect filamentous tau in vivo...
  4. doi request reprint 100 years of Lewy pathology
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Nat Rev Neurol 9:13-24. 2013
    ..In this article, we review the relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders...
  5. pmc Stimulation of autophagy reduces neurodegeneration in a mouse model of human tauopathy
    Veronique Schaeffer
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Brain 135:2169-77. 2012
    ..Our findings provide direct evidence in favour of the degradation of tau aggregates by autophagy. Activation of autophagy may be worth investigating in the context of therapies for human tauopathies...
  6. pmc alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies
    M G Spillantini
    Medical Research Council Centre for Brain Repair and Department of Neurology, University of Cambridge, Robinson Way, Cambridge CB2 2PY, United Kingdom
    Proc Natl Acad Sci U S A 95:6469-73. 1998
    ..These findings indicate that alpha-synuclein forms the major filamentous component of Lewy bodies and Lewy neurites...
  7. ncbi request reprint Parkinson's disease and other alpha-synucleinopathies
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Clin Chem Lab Med 39:308-12. 2001
    ..They are not present in the pathological filamentous lesions and have not been found to be linked to genetic disease. The new work has established the alpha-synucleinopathies as a major class of neurodegenerative disease...
  8. ncbi request reprint The significance of tau and alpha-synuclein inclusions in neurodegenerative diseases
    M Goedert
    MRC Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK
    Curr Opin Genet Dev 11:343-51. 2001
    ..Building on previous work, synthetic alpha-synuclein filaments have been shown to exhibit the characteristics of amyloid...
  9. pmc From genetics to pathology: tau and alpha-synuclein assemblies in neurodegenerative diseases
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Philos Trans R Soc Lond B Biol Sci 356:213-27. 2001
    ....
  10. ncbi request reprint Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Their relevance for understanding the neurogenerative process
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Ann N Y Acad Sci 920:74-83. 2000
    ..The new work has shown that dysfunction of tau protein causes neurodegeneration...
  11. ncbi request reprint Filamentous nerve cell inclusions in neurodegenerative diseases
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Curr Opin Neurobiol 8:619-32. 1998
    ....
  12. pmc The tauopathies: toward an experimental animal model
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Am J Pathol 154:1-6. 1999
  13. ncbi request reprint Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 450:306-11. 1999
    ..These findings indicate that missense mutations in tau lead to frontotemporal dementia through potentially multiple mechanisms...
  14. pmc Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Philos Trans R Soc Lond B Biol Sci 354:1101-18. 1999
    ..The formation of intracellular filamentous inclusions might be the gain of toxic function that leads to the demise of affected brain cells...
  15. doi request reprint The propagation of prion-like protein inclusions in neurodegenerative diseases
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    Trends Neurosci 33:317-25. 2010
    ....
  16. ncbi request reprint Tau mutations in frontotemporal dementia FTDP-17 and their relevance for Alzheimer's disease
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Biochim Biophys Acta 1502:110-21. 2000
    ..Several missense mutations also have a stimulatory effect on heparin-induced tau filament formation. Assembly of tau into filaments may be the gain of toxic function that is believed to underlie the demise of affected brain cells...
  17. ncbi request reprint Frontotemporal lobar degeneration through loss of progranulin function
    Michel Goedert
    MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, UK
    Brain 129:2808-10. 2006
  18. ncbi request reprint A century of Alzheimer's disease
    Michel Goedert
    Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 2QH, UK
    Science 314:777-81. 2006
    ..Genetic studies have shown that dysfunction of amyloid-beta or tau is sufficient to cause dementia. The ongoing molecular dissection of the neurodegenerative pathways is expected to lead to a true understanding of disease pathogenesis...
  19. ncbi request reprint Alois Alzheimer: his life and times
    Michel Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Brain Pathol 17:57-62. 2007
    ..His name will always be linked with the form of dementia that he described 100 years ago. Here we mark this anniversary by discussing Alzheimer's contributions to dementia research in the context of his life and times...
  20. ncbi request reprint Tau protein and neurodegeneration
    Michel Goedert
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Semin Cell Dev Biol 15:45-9. 2004
    ..At an experimental level, the new understanding is leading to the development of good transgenic animal models of the tauopathies...
  21. pmc Neurodegenerative tauopathy in the worm
    Michel Goedert
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Proc Natl Acad Sci U S A 100:9653-5. 2003
  22. pmc Oskar Fischer and the study of dementia
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    Brain 132:1102-11. 2009
    ..Although much has been written about Alzheimer, only little is known about Fischer. The present article discusses Fischer's work on dementia in the context of his life and time...
  23. doi request reprint Pathogenesis of the tauopathies
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK
    J Mol Neurosci 45:425-31. 2011
    ..This is consistent with the existence of multiple tau conformers and recent findings have provided experimental support for this concept...
  24. pmc Structure of tau exon 10 splicing regulatory element RNA and destabilization by mutations of frontotemporal dementia and parkinsonism linked to chromosome 17
    L Varani
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 96:8229-34. 1999
    ..By exon trapping, the reduction in thermodynamic stability is correlated with increased splicing in of exon 10...
  25. pmc Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 16:3563-71. 1997
    ..Unlike SAPK2a and SAPK2b, SAPK4 and SAPK3 were not inhibited by the drugs SB 203580 and SB 202190. Our results suggest that cellular functions previously attributed to SAPK1 and/or SAPK2 may be mediated by SAPK3 or SAPK4...
  26. ncbi request reprint Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 409:57-62. 1997
    ..These findings double the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders...
  27. ncbi request reprint Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition
    M Hasegawa
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    J Biol Chem 274:12626-31. 1999
    ..Phosphorylation of a PDZ domain-containing protein by an associated protein kinase is a novel mechanism for determining both the localization and the substrate specificity of a protein kinase...
  28. ncbi request reprint Human synaptotagmin V (SYT5): sequence, genomic structure, and chromosomal location
    M Craxton
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, United Kingdom
    Genomics 42:165-9. 1997
    ..4 by PCR analysis of somatic cell hybrid DNA and by DNA hybridization to arrayed cosmids of the chromosome 19 metric physical map. This provides the first report of linked synaptotagmin genes...
  29. pmc Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Biochem J 301:871-7. 1994
    ..This result contrasts with previous studies of Ser-202 and Ser-396 which are partially phosphorylated in fetal tau, unphosphorylated in adult tau but almost fully phosphorylated in PHF tau...
  30. ncbi request reprint Tau gene mutation K257T causes a tauopathy similar to Pick's disease
    C Rizzini
    Brain Repair Centre and Department of Neurology, University of Cambridge, United Kingdom
    J Neuropathol Exp Neurol 59:990-1001. 2000
    ..Taken together, the present findings indicate that the K257T mutation in Tau can cause a dementing condition similar to Pick's disease...
  31. ncbi request reprint Alternative splicing of synaptotagmins involving transmembrane exon skipping
    M Craxton
    Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    FEBS Lett 460:417-22. 1999
    ..Although the expression of most synaptotagmins predominates in neural tissue, we find that by contrast, synaptotagmin 6 is more abundant in thymus...
  32. ncbi request reprint Identification of two distinct synucleins from human brain
    R Jakes
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 345:27-32. 1994
    ..We refer to the 140 and 134 amino acid proteins as alpha-synuclein and beta-synuclein, respectively. Both synucleins are expressed predominantly in brain, where they are concentrated in presynaptic nerve terminals...
  33. ncbi request reprint PTL-1, a microtubule-associated protein with tau-like repeats from the nematode Caenorhabditis elegans
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    J Cell Sci 109:2661-72. 1996
    ..These findings indicate that MAPs of the tau/MAP2/MAP4 family are found throughout much of the animal kingdom, where they may play a role in specialised processes requiring microtubules...
  34. pmc Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
    M G Spillantini
    Medical Research Council Centre for Brain Repair and Department of Neurology, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK
    Proc Natl Acad Sci U S A 95:7737-41. 1998
    ..The results show that dysregulation of tau protein production can cause neurodegeneration and imply that the FTDP-17 gene is the tau gene. This work has major implications for Alzheimer's disease and other tauopathies...
  35. ncbi request reprint Assignment of the human stress-activated protein kinase-3 gene (SAPK3) to chromosome 22q13.3 by fluorescence in situ hybridization
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Genomics 41:501-2. 1997
  36. pmc Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 8:393-9. 1989
    ..Taken in conjunction with previous findings, the present results indicate that both the three and four repeat-containing tau protein isoforms are present in the core of the paired helical filament...
  37. ncbi request reprint Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
    M Goedert
    Medical Research Council, Laboratory of Molecular Biology, Cambridge, England
    Neuron 3:519-26. 1989
    ..Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease...
  38. pmc Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments
    M G Spillantini
    Medical Research Council Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 94:4113-8. 1997
    ....
  39. pmc Different configurational states of beta-amyloid and their distributions relative to plaques and tangles in Alzheimer disease
    M G Spillantini
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 87:3947-51. 1990
    ..These antibodies, in conjunction with anti-tau antibodies, were used to demonstrate a close spatial relationship between amyloid deposits and neurofibrillary tangles...
  40. ncbi request reprint SAP kinase-3, a new member of the family of mammalian stress-activated protein kinases
    S Mertens
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 383:273-6. 1996
    ..Transcripts encoding stress-activated protein kinase-3 are widely expressed, with high levels in skeletal muscle...
  41. pmc Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 85:4051-5. 1988
    ....
  42. ncbi request reprint The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy
    M G Spillantini
    Department of Neurology and Brain Repair Centre, University of Cambridge, Cambridge, UK
    Ann N Y Acad Sci 920:16-27. 2000
    ..The new work has established the alpha-synucleinopathies as a major class of neurodegenerative disease...
  43. ncbi request reprint Protein phosphatase 2A is the major enzyme in brain that dephosphorylates tau protein phosphorylated by proline-directed protein kinases or cyclic AMP-dependent protein kinase
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, England
    J Neurochem 65:2804-7. 1995
    ..We show that protein phosphatase 2A is by far the major protein phosphatase activity in brain that dephosphorylates tau phosphorylated in this manner...
  44. ncbi request reprint Microtubule-associated protein tau, heparan sulphate and alpha-synuclein in several neurodegenerative diseases with dementia
    M G Spillantini
    MRC Brain Repair Centre and Department of Neurology, University of Cambridge, UK
    Acta Neuropathol 97:585-94. 1999
    ....
  45. ncbi request reprint A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies
    M G Spillantini
    Brain Repair Centre, University of Cambridge, UK
    Ann Neurol 48:939-43. 2000
    ..By exon trapping, the mutation produced an increase in the splicing in of exon 10, indicating that it probably causes disease through an overproduction of four-repeat tau...
  46. pmc Cloning of a big tau microtubule-associated protein characteristic of the peripheral nervous system
    M Goedert
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 89:1983-7. 1992
    ....
  47. ncbi request reprint Synaptotagmin V: a novel synaptotagmin isoform expressed in rat brain
    M Craxton
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 361:196-200. 1995
    ..It is expressed at high levels in rat brain, but not in spinal cord or a number of peripheral non-neuronal tissues...
  48. ncbi request reprint Molecular characterization of microtubule-associated proteins tau and MAP2
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Trends Neurosci 14:193-9. 1991
    ..Messenger RNAs for MAP2 of high molecular mass are expressed both in cell bodies and in dendrites, consistent with the dendritic localization of the corresponding protein isoforms...
  49. ncbi request reprint p42 MAP kinase phosphorylation sites in microtubule-associated protein tau are dephosphorylated by protein phosphatase 2A1. Implications for Alzheimer's disease [corrected]
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge, UK
    FEBS Lett 312:95-9. 1992
    ..Of the major serine/threonine protein phosphatases found in mammalian tissues only protein phosphatase 2A (PP2A) could dephosphorylate tau phosphorylated in this manner, with PP2A1 being the most effective form of the enzyme...
  50. ncbi request reprint Localization of the human kinesin light chain gene (KNS2) to chromosome 14q32.3 by fluorescence in situ hybridization
    M Goedert
    MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    Genomics 32:173-5. 1996
  51. pmc Nerve growth factor mRNA and protein increase in hypothalamus in a mouse model of aggression
    M G Spillantini
    Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 86:8555-9. 1989
    ..The present results firmly establish that nerve cells constitute the major source in NGF in the brain. They also open the way to understanding the regulation of NGF biosynthesis in the central nervous system...
  52. ncbi request reprint Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35
    M G Spillantini
    MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
    Genomics 27:379-81. 1995
  53. ncbi request reprint The mas oncogene encodes an angiotensin receptor
    T R Jackson
    Medical Research Council Molecular Neurobiology Unit, Cambridge, UK
    Nature 335:437-40. 1988
    ..The mas oncogene product was transiently expressed in Xenopus oocytes, and stably expressed in a transfected mammalian cell line. The results demonstrate that the mas gene product is a functional angiotensin receptor...
  54. pmc Interaction of tau protein with the dynactin complex
    Enrico Magnani
    Department of Clinical Neurosciences, Brain Repair Centre, University of Cambridge, Cambridge, UK
    EMBO J 26:4546-54. 2007
    ..These findings, which suggest a direct involvement of tau in axonal transport, have implications for understanding the pathogenesis of tauopathies...
  55. ncbi request reprint Synuclein proteins of the pufferfish Fugu rubripes: sequences and functional characterization
    Hirotaka Yoshida
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Biochemistry 45:2599-607. 2006
    ..Filament assembly of synucleins was directly proportional to their degree of hydrophobicity and their tendency to form beta-sheet structure, and correlated inversely with their net charge...
  56. pmc Cell-cycle markers in a transgenic mouse model of human tauopathy: increased levels of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1
    Patrice Delobel
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Am J Pathol 168:878-87. 2006
    ..Thus, reactivation of the cell cycle was not involved in tau hyperphos-phorylation and filament formation, consistent with expression of p21Cip1 and p27Kip1 in tangle-bearing nerve cells...
  57. pmc White matter tauopathy with globular glial inclusions: a distinct sporadic frontotemporal lobar degeneration
    Gabor G Kovacs
    Institute of Neurology, Medical University of Vienna, Vienna, Austria
    J Neuropathol Exp Neurol 67:963-75. 2008
    ..This type of tauopathy with GGIs expands the group of neurodegenerativedisorders in which oligodendroglial pathology predominates, beyond the synucleinopathy multiple system atrophy disorders...
  58. ncbi request reprint Sequential phosphorylation of tau protein by cAMP-dependent protein kinase and SAPK4/p38delta or JNK2 in the presence of heparin generates the AT100 epitope
    Hirotaka Yoshida
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    J Neurochem 99:154-64. 2006
    ..Phosphorylation by PKA and SAPK4/p38delta abolished the ability of tau to promote microtubule assembly, but failed to influence significantly the heparin-induced assembly of tau into filaments...
  59. doi request reprint The value of incomplete mouse models of Alzheimer's disease
    Rebecca Radde
    Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, Otfried Muller Strasse 27, Tubingen, Germany
    Eur J Nucl Med Mol Imaging 35:S70-4. 2008
    ....
  60. pmc Analysis of tau phosphorylation and truncation in a mouse model of human tauopathy
    Patrice Delobel
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 OQH, UK
    Am J Pathol 172:123-31. 2008
    ..The late appearance and low abundance of tau ending at D421 indicate that it is unlikely that truncation at this site is necessary for the assembly of tau into filaments...
  61. ncbi request reprint The novel Tau mutation G335S: clinical, neuropathological and molecular characterization
    Salvatore Spina
    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive MS A138, Indianapolis, IN, 46202, USA
    Acta Neuropathol 113:461-70. 2007
    ..Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments...
  62. pmc A simple algorithm locates beta-strands in the amyloid fibril core of alpha-synuclein, Abeta, and tau using the amino acid sequence alone
    Shahin Zibaee
    Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom
    Protein Sci 16:906-18. 2007
    ..As before, the output of the algorithm, in the form of a simple x-y plot, was found to correlate very well with the location of alpha-helical structure in membrane bilayer-associated alpha-syn...
  63. pmc The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family
    Salvatore Spina
    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
    Brain 131:72-89. 2008
    ..This multidisciplinary study provides a comprehensive description of the natural history of disease in one of the largest known families with FTDP-17T...
  64. ncbi request reprint Phosphorylation of human microtubule-associated protein tau by protein kinases of the AGC subfamily
    Kanwar Virdee
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK
    FEBS Lett 581:2657-62. 2007
    ..MSK1 phosphorylated S214, as well as S262, a KXGS site in the first repeat, and S305 in the second repeat...
  65. ncbi request reprint Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies
    Aasami Ishii
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    FEBS Lett 581:4711-7. 2007
    ..Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies...
  66. ncbi request reprint Mutations in the tau gene (MAPT) in FTDP-17: the family with Multiple System Tauopathy with Presenile Dementia (MSTD)
    Maria Grazia Spillantini
    Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK
    J Alzheimers Dis 9:373-80. 2006
    ..Proc. Natl. Acad. Sci. USA 95, 7737-7741] reported a mutation at position + 3 in the intron following alternatively spliced exon 10 of the tau gene in a family...
  67. ncbi request reprint Variable phenotypic expression and extensive tau pathology in two families with the novel tau mutation L315R
    Esther van Herpen
    Department of Clinical Genetics, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
    Ann Neurol 54:573-81. 2003
    ..All six tau isoforms were present in soluble brain tau. Recombinant tau proteins with the L315R mutation showed a reduced ability to promote microtubule assembly...
  68. ncbi request reprint A novel tau mutation, S320F, causes a tauopathy with inclusions similar to those in Pick's disease
    Sonia M Rosso
    Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
    Ann Neurol 51:373-6. 2002
    ..Recombinant tau protein with the S320F mutation showed a greatly reduced ability to promote microtubule assembly...
  69. ncbi request reprint Functional effects of tau gene mutations deltaN296 and N296H
    Hirotaka Yoshida
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    J Neurochem 80:548-51. 2002
    ..By exon trapping, they increased the splicing of exon 10. DeltaN296 and N296H thus define a class of tau mutations with effects at both the RNA and the protein level...
  70. pmc Stress- and mitogen-induced phosphorylation of the synapse-associated protein SAP90/PSD-95 by activation of SAPK3/p38gamma and ERK1/ERK2
    Guadalupe Sabio
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 380:19-30. 2004
    ....
  71. ncbi request reprint Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases in intact cells
    Valérie Buée-Scherrer
    Medical Research Council Laboratory of Molecular Biology, Hills Road, CB2 2QH, Cambridge, UK
    FEBS Lett 515:151-4. 2002
    ..These findings indicate that the aberrant activation of SAP kinases, especially SAPK3/p38gamma and SAPK4/p38delta, could play an important role in the abnormal hyperphosphorylation of tau that is an invariant feature of the tauopathies...
  72. pmc Tau filaments from human brain and from in vitro assembly of recombinant protein show cross-beta structure
    John Berriman
    Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 100:9034-8. 2003
    ..Using both these approaches, we show here that native filaments from brain and filaments assembled in vitro from expressed tau protein have a clear cross-beta structure...
  73. pmc Repeat motifs of tau bind to the insides of microtubules in the absence of taxol
    Santwana Kar
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    EMBO J 22:70-7. 2003
    ..We propose that loops in bound tau stabilize microtubules in a similar way to taxol, although with lower affinity so that assembly is reversible...
  74. ncbi request reprint Molecular cloning and functional characterization of chicken brain tau: isoforms with up to five tandem repeats
    Hirotaka Yoshida
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, U K
    Biochemistry 41:15203-11. 2002
    ..The 34 amino acid insert positively influences both the rate and the extent of microtubule assembly, whereas the 53 amino acid insert only influences the extent of assembly...
  75. ncbi request reprint Abundant tau filaments and nonapoptotic neurodegeneration in transgenic mice expressing human P301S tau protein
    Bridget Allen
    Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom
    J Neurosci 22:9340-51. 2002
    ..No evidence for apoptosis was obtained, despite the extensive colocalization of hyperphosphorylated tau protein with activated MAP kinase family members. The latter may be involved in the hyperphosphorylation of tau...
  76. ncbi request reprint Phosphorylation of microtubule-associated protein tau by isoforms of c-Jun N-terminal kinase (JNK)
    Hirotaka Yoshida
    MRC Laboratory of Molecular Biology, Cambridge, UK
    J Neurochem 90:352-8. 2004
    ..These findings extend the number of candidate protein kinases for the hyperphosphorylation of tau in Alzheimer's disease and other neurodegenerative disorders...
  77. ncbi request reprint Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of alpha-synuclein assembly by beta- and gamma-synucleins
    Vladimir N Uversky
    Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA
    J Biol Chem 277:11970-8. 2002
    ..The lack of fibrils formed by beta-synuclein is most readily explained by the absence of a stretch of hydrophobic residues from the middle region of the protein. A model for the inhibition is proposed...
  78. ncbi request reprint Evidence that phosphorylation of the microtubule-associated protein Tau by SAPK4/p38delta at Thr50 promotes microtubule assembly
    Carmen Feijoo
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    J Cell Sci 118:397-408. 2005
    ..These findings suggest a role for Tau in the adaptative response of neurons to stress and indicate that SAPK4/p38delta and/or SAPK3/p38delta may contribute to the hyperphosphorylation of Tau in the human tauopathies...
  79. ncbi request reprint Functional characterization of FTDP-17 tau gene mutations through their effects on Xenopus oocyte maturation
    Patrice Delobel
    INSERM U422, Institut de Médecine Prédictive et Recherche Thérapeutique, 59045 Lille, France
    J Biol Chem 277:9199-205. 2002
    ..Those findings establish Xenopus oocyte maturation as a system allowing the study of the functional effects of tau gene mutations in a quantitative manner...
  80. ncbi request reprint Mutations causing neurodegenerative tauopathies
    Michel Goedert
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Biochim Biophys Acta 1739:240-50. 2005
    ....
  81. ncbi request reprint Inhibition of heparin-induced tau filament formation by phenothiazines, polyphenols, and porphyrins
    Sayuri Taniguchi
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, Tokyo Metropolitan Organization for Medical Research, 2 1 8 Kamikitazawa, Setagaya Ku, Tokyo 156 8585, Japan
    J Biol Chem 280:7614-23. 2005
    ..Identification of small molecule inhibitors of heparin-induced assembly of tau will form a starting point for the development of mechanism-based therapies for the tauopathies...
  82. pmc Induction of inflammatory mediators and microglial activation in mice transgenic for mutant human P301S tau protein
    Arianna Bellucci
    Brain Repair Centre, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK
    Am J Pathol 165:1643-52. 2004
    ..These findings suggest that inflammation may play a significant role in the events leading to neurodegeneration in the tauopathies and that anti-inflammatory compounds may have therapeutic potential...
  83. ncbi request reprint Mutation E46K increases phospholipid binding and assembly into filaments of human alpha-synuclein
    Woong Choi
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    FEBS Lett 576:363-8. 2004
    ..The observed effects on lipid binding and filament assembly may explain the pathogenic nature of the E46K mutation in alpha-synuclein...
  84. ncbi request reprint Tau gene (MAPT) sequence variation among primates
    Max Holzer
    MRC Laboratory of Molecular Biology, Cambridge, UK
    Gene 341:313-22. 2004
    ..Sequencing of Saitohin revealed an intact open reading frame in chimpanzee and gorilla, but not in gibbon or macaque...
  85. ncbi request reprint A Raman optical activity study of rheomorphism in caseins, synucleins and tau. New insight into the structure and behaviour of natively unfolded proteins
    Christopher D Syme
    Department of Chemistry, University of Glasgow, UK
    Eur J Biochem 269:148-56. 2002
    ....
  86. ncbi request reprint Proteasomal degradation of tau protein
    Della C David
    Cambridge Centre for Brain Repair and Neurology Department, University of Cambridge, Cambridge, UK
    J Neurochem 83:176-85. 2002
    ..Our results are consistent with an in vivo role for the proteasome in tau degradation and support the existence of ubiquitin-independent pathways for the proteasomal degradation of unfolded proteins...
  87. pmc In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain
    Liang Ye
    GlaxoSmithKline, Clinical Science and Technology, Neurology DM, New Frontiers Science Park, Harlow, UK
    J Neurochem 105:1428-37. 2008
    ..Lewy bodies pathology is therefore unlikely to contribute significantly to the retention of PIB in positron emission tomography imaging studies...
  88. pmc p38gamma regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP
    Guadalupe Sabio
    MRC Protein Phosphorylation Unit, University of Dundee, Dundee, UK
    EMBO J 24:1134-45. 2005
    ..This is likely to regulate the integrity of intercellular-junctional complexes, and cell shape and volume in response to osmotic stress...
  89. ncbi request reprint GSK3 inhibitors: development and therapeutic potential
    Philip Cohen
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Nat Rev Drug Discov 3:479-87. 2004
  90. ncbi request reprint Early-onset dementia with Lewy bodies
    Masaki Takao
    Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Drive, B029D, Indianapolis, IN 46202, USA
    Brain Pathol 14:137-47. 2004
    ..This study provides further evidence of the clinical and pathological heterogeneity of DLB...
  91. ncbi request reprint Alpha-synuclein adopts an alpha-helical conformation in the presence of polyunsaturated fatty acids to hinder micelle formation
    Kerensa Broersen
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Biochemistry 45:15610-6. 2006
    ..These results identify a potential biological function for alpha-synuclein and define an omega-3-linked pathway leading to alpha-synuclein aggregation...
  92. ncbi request reprint Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders
    George K Tofaris
    Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2PY, United Kingdom
    J Neurosci 26:3942-50. 2006
    ..These findings suggest that the C-terminal of alpha-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders and multiple system atrophy...
  93. ncbi request reprint Cysteine misincorporation in bacterially expressed human alpha-synuclein
    Masami Masuda
    Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2 1 8 Kamikitazawa, Setagaya ku 156 8585, Tokyo, Japan
    FEBS Lett 580:1775-9. 2006
    ..To avoid potential artefacts, we recommend use of the Y136-TAT construct for the expression of human alpha-syn...
  94. ncbi request reprint Sequence Determinants for Amyloid Fibrillogenesis of Human alpha-Synuclein
    Shahin Zibaee
    MRC Laboratory of Molecular Biology, Cambridge, CB2 0QH, UK
    J Mol Biol 374:454-64. 2007
    ..The combination of these simple physicochemical properties with a previously described calculation of beta-strand contiguity allowed us to design mutations that changed the fibrillogenic propensity of alpha-synuclein in predictable ways...