A5048411689- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- RNA regulation and disease
- HIV Research and Treatment
- Alzheimer's disease research and treatments
- Retinal Development and Disorders
- Bacteriophages and microbial interactions
- Immune Response and Inflammation
- Animal Disease Management and Epidemiology
- Clusterin in disease pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- NF-κB Signaling Pathways
- Alcoholism and Thiamine Deficiency
- Neuroscience and Neuropharmacology Research
- biodegradable polymer synthesis and properties
- Biotin and Related Studies
- RNA Research and Splicing
- Ocular Disorders and Treatments
- Retinal and Macular Surgery
- Neurological disorders and treatments
CureVac (Germany)
2024
Light Chain Bioscience (Switzerland)
2017-2022
University of Zurich
2000-2022
Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie
2022
Paul Ehrlich Institut
2005-2009
University Hospital of Zurich
2001-2005
Charité - Universitätsmedizin Berlin
2002
Technical University of Munich
2002
In scrapie-infected mice, prions are found associated with splenic but not circulating B and T lymphocytes in the stroma, which contains follicular dendritic cells (FDCs). Formation maintenance of mature FDCs require presence expressing membrane-bound lymphotoxin-alpha/beta. Treatment mice soluble lymphotoxin-beta receptor results disappearance from spleen. We show that this treatment abolishes prion accumulation retards neuroinvasion after intraperitoneal scrapie inoculation. These data...
Aggregation of α-synuclein (α-syn) is neuropathologically and genetically linked to Parkinson's disease (PD). Since stereotypic cell-to-cell spreading α-syn pathology believed contribute progression, immunotherapy with antibodies directed against considered a promising therapeutic approach for slowing progression. Here we report the identification, binding characteristics, efficacy in PD mouse models human-derived antibody BIIB054, which currently under investigation Phase 2 clinical trial...
Variant Creutzfeldt–Jakob disease and scrapie are typically initiated by extracerebral exposure to prions, exhibit early prion accumulation in germinal centers. Follicular dendritic cells (FDCs), whose development maintenance centers depends on tumor necrosis factor (TNF) lymphotoxin (LT) signaling, thought be indispensable for extraneural pathogenesis. Here, we administered prions intraperitoneally mice deficient TNF LT signaling components. LTα −/− , LTβ LTβR × TNFα resisted infection...
Mutations in the gene encoding superoxide dismutase 1 (SOD1) lead to misfolding and aggregation of SOD1 cause familial amyotrophic lateral sclerosis (FALS). However, implications wild-type sporadic forms ALS (SALS) remain unclear. By screening human memory B cells from a large cohort healthy elderly subjects, we generated recombinant monoclonal antibody (α-miSOD1) that selectively bound misfolded SOD1, but not physiological dimers. On postmortem spinal cord sections 121 patients with ALS,...
Prion replication in spleen and neuroinvasion after i.p. inoculation of mice is impaired forms immunodeficiency where mature B lymphocytes are lacking. In spleens wild-type mice, infectivity associated with T stroma but not circulating lymphocytes. We generated transgenic prion protein knockout overexpressing found that they failed to accumulate prions inoculation. conclude splenic prion-replication competent acquire from other cells, most likely follicular dendritic cells which closely...
ABSTRACT Passive immunization with antibodies directed against the cellular form of prion protein (PrP C ) can protect disease. However, active recombinant has so far failed to induce native PrP expressed on cell surface. To develop an antiprion vaccine, a retroviral display system presenting either full-length mouse (PrP209) or C-terminal 111 amino acids (PrP111) fused transmembrane domain platelet-derived growth factor receptor was established. Western blot analysis and immunogold electron...
Cellular prion protein (PrPc) is a physiological constituent of eukaryotic cells. The cellular pathways underlying prions spread from the sites infection/peripheral replication to central nervous system are still not elucidated. Membrane-derived microvesicles (MVs) submicron (0.1–1 µm) particles, that released by cells during plasma membrane shedding processes. They usually liberated different cell types, mainly upon activation as well apoptosis, in this case, one their hallmarks exposure...
Abstract Affinity maturation and Ab class switches occur in lymphoid germinal centers (GCs), which differentiation maintenance depend on lymphotoxin (LT) signaling include of follicular dendritic cells (FDCs). The events leading to FDC GC are poorly defined. Using several approaches functional genomics, we enumerated transcripts affected mice by suppressing LT β receptor (LTβR) and/or overrepresented FDC-enriched isolates. Protein expression analysis 3 12 genes both enriched FDCs...
Conference Abstract| October 01 2000 Molecular Biology of Prion Disease C. Weissmann; Weissmann 1Imperial College School Medicine, Norfolk Place, London Search for other works by this author on: This Site PubMed Google Scholar F. Montrasio; Montrasio *Institute Neuropathology, University Zuerich A. Aguzzi Biochem Soc Trans (2000) 28 (5): A126. https://doi.org/10.1042/bst028a126b Views Icon Article contents Figures & tables Video Audio Supplementary Data Peer Review Share MailTo Twitter...
Within the CNS, normal form of cellular prion protein (PrP C ) is expressed on neurons, oligodendrocytes, and astrocytes. The contribution these cell types to replication pathogenesis unclear. To assess role we PrP under control myelin basic (MBP) promoter in mice lacking endogenous . was detected oligodendrocytes Schwann cells but not neurons MBP-PrP never developed scrapie after intracerebral, intraperitoneal, or intraocular challenge with prions. Transgenic brains did contain...
Messenger RNA (mRNA)–based therapies are a promising approach to medical treatment. Except for infectious diseases, no other disease has mRNA-based available. The eye is an ideal model mRNA therapeutic development because it requires limited dosing. Proliferative vitreoretinopathy (PVR) blinding condition caused by retinal detachment that now lacks available treatment, with surgery as the only treatment option. We previously implicated runt-related transcription factor-1 (RUNX1) driver of...
Some of the early events following scrapie infection take place in lymphoreticular system (LRS) and result significant replication prions lymphoid organs. The identity cells LRS that produce their role neuroinvasion are still unknown. We find spleen scrapie-infected mice, associated with T B to a somewhat lesser degree stroma, which contains follicular dendritic (FDC's); curiously, no infectivity was found lymphocytes from blood same mice. Thus, splenic either replicate or acquire them...
Hexanucleotide G 4 C 2 repeat expansions in the C9orf72 gene are most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Dipeptide proteins (DPRs) generated by translation repeat-containing RNAs show toxic effects vivo as well vitro key targets for therapeutic intervention. We human antibodies that bind DPRs with high affinity specificity. Anti-GA engaged extra- intra-cellular poly-GA reduced aggregate formation a overexpressing cell line. However, antibody...
Abstract The cellular prion protein (PrP C ) is a highly conserved glycoprotein of unknown biological function. To gain insight into the physiological role PrP , we generated novel knockout cell line, named o/o ML, by immortalization neuroepithelial precursor cells derived from cerebellum PrP‐knockout mice using temperature‐sensitive simian virus 40 (SV40) large T antigen. We demonstrated that ML line unipotent with glutamatergic properties, which can acquire neuronal features when...
Passive immunization with antibodies directed against the cellular form of prion protein can protect disease. However, so far active recombinant failed to induce in vivo protective (PrP)-specific antibody responses.