A5030636499- Alzheimer's disease research and treatments
- Prion Diseases and Protein Misfolding
- Parkinson's Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Microtubule and mitosis dynamics
- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Bacteriophages and microbial interactions
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- Nuclear Receptors and Signaling
- Hepatitis B Virus Studies
- Connective tissue disorders research
- Cellular transport and secretion
- Enzyme Structure and Function
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Virus-based gene therapy research
- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
MRC Laboratory of Molecular Biology
2013-2023
Medical Research Council
2005-2023
Medical University of Vienna
2008
Queen Mary University of London
2008
Indiana University Bloomington
2007
University of Cambridge
1987-2006
University of Copenhagen
2003
MRC Prion Unit
2003
Holbæk Sygehus
2003
State Key Laboratory of Molecular Biology
2003
Lewy bodies and neurites are the defining neuropathological characteristics of Parkinson’s disease dementia with bodies. They made abnormal filamentous assemblies unknown composition. We show here that from stained strongly by antibodies directed against amino-terminal carboxyl-terminal sequences α-synuclein, showing presence full-length or close to α-synuclein. The number α-synuclein-stained structures exceeded immunoreactive for ubiquitin, which is currently most sensitive marker neurites....
Screening of cDNA libraries prepared from the frontal cortex an Alzheimer disease patient and fetal human brain has led to isolation for a core protein paired helical filament disease. The partial amino acid sequence this was used design synthetic oligonucleotide probes. encodes 352 acids that contains characteristic repeat in its carboxyl-terminal half. This is highly homologous mouse microtubule-associated tau thus constitutes equivalent tau. RNA blot analysis indicates presence two major...
Filamentous inclusions made of hyperphosphorylated tau are characteristic numerous human neurodegenerative diseases, including Alzheimer’s disease, tangle-only dementia, Pick argyrophilic grain disease (AGD), progressive supranuclear palsy, and corticobasal degeneration. In AGD, it has been shown that filamentous appears to spread in a stereotypic manner as the progresses. We previously demonstrated injection brain extracts from mutant P301S tau-expressing transgenic mice into brains for...
The identification of mutations in the Tau gene frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has made it possible express human tau protein with pathogenic transgenic animals. Here we report on production characterization a line mice for 383 aa isoform P301S mutation. At 5-6 months age, homozygous animals from this developed neurological phenotype dominated by severe paraparesis. According light microscopy, many nerve cells brain spinal cord were strongly...
The paired helical filament, the principal constituent of neurofibrillary tangles characteristic Alzheimer disease, is shown to consist two structurally distinct parts. An external fuzzy region can be removed by Pronase treatment leave a Pronase-resistant morphologically recognizable core. Scanning transmission electron microscopy gives an estimate for mass per unit length as 79 kDa.nm-1 before and 65 after treatment. carries all epitopes recognized different antisera against...
Tau is a neuronal phosphoprotein whose expression developmentally regulated. A single tau isoform expressed in fetal human brain but six isoforms are adult brain, with the corresponding to shortest of isoforms. Phosphorylation also regulated, as phosphorylated at more sites than tau. In Alzheimer disease, become abnormally and form paired helical filament, major fibrous component characteristic neurofibrillary lesions. We show here that Ser-202 (in numbering longest isoform) phosphorylation...
Recently two point mutations in the alpha-synuclein gene have been found familial Parkinson's disease. The characteristic fibrous neuropathological lesions of and other neurodegenerative diseases shown to stain strongly with antibodies against extracted filaments labelled anti-alpha-synuclein antibodies. In view close involvement pathology, it was important establish an vitro assembly system. We report here that C-terminally truncated recombinant readily assembles into resembling those...
Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer’s and Pick’s Here, we used cryo- immuno- electron microscopy to characterise that were assembled from recombinant full-length human with four (2N4R) or three (2N3R) microtubule-binding repeats the presence heparin. 2N4R assembles multiple types filaments, structures reveal similar ‘kinked hairpin’ folds, which second...
Tau is a neuronal phosphoprotein the expression of which developmentally regulated. A single tau isoform expressed in fetal human brain but six isoforms are adult brain, with corresponding to shortest isoform. Phosphorylation also regulated, as phosphorylated at more sites than tau. In Alzheimer's disease, become hyperphosphorylated and form paired helical filament (PHF), major fibrous component neurofibrillary lesions. One way identify use antibodies that recognize residues within specific...
Neurofibrillary lesions made of hyperphosphorylated microtubule-associated protein tau constitute not only one the defining neuropathological features Alzheimer disease but also are present in a number other neurodegenerative diseases with dementia. Here we describe novel autosomal dominant named familial "multiple system tauopathy presenile dementia," which is characterized by abundant fibrillary deposits both neurons and glial cells. There no detectable beta-amyloid. The form twisted...
The presence of abundant neurofibrillary tangles in certain areas the brain constitutes one defining pathological characteristics Alzheimer disease. predominant component tangle is an abnormal fibrous assembly known as paired helical filament (PHF). PHF formed by a twisted double-helical ribbon subunits that gives rise to image alternating width between 8 nm and 20 with cross-over spacing 80 nm. Also found straight (SF), different kind filament, about 15 wide, does not exhibit marked...