A5080687016- Prion Diseases and Protein Misfolding
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Neurological diseases and metabolism
- Neurogenetic and Muscular Disorders Research
- Trace Elements in Health
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- Bioactive Compounds and Antitumor Agents
- RNA modifications and cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Psidium guajava Extracts and Applications
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Essential Oils and Antimicrobial Activity
- Infectious Encephalopathies and Encephalitis
- Bacterial biofilms and quorum sensing
- Viral Infections and Immunology Research
- S100 Proteins and Annexins
- Inflammasome and immune disorders
- Receptor Mechanisms and Signaling
University of Zurich
2016-2025
Quantitative BioSciences
2020-2024
Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie
2022
ETH Zurich
2018
Life Science Zurich
2018
Ludwig Cancer Research
2013
Ludwig Cancer Research
2008-2013
University of California, San Diego
2008-2013
University Hospital of Zurich
2004-2012
Cornell University
2008
Expanded hexanucleotide repeats in the chromosome 9 open reading frame 72 (C9orf72) gene are most common genetic cause of ALS and frontotemporal degeneration (FTD). Here, we identify nuclear RNA foci containing expansion (GGGGCC) patient cells, including white blood fibroblasts, glia, multiple neuronal cell types (spinal motor, cortical, hippocampal, cerebellar neurons). not present sporadic ALS, familial ALS/FTD caused by other mutations (SOD1, TDP-43, or tau), Parkinson disease,...
Transactivating response region DNA binding protein (TDP-43) is the major component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with inclusions. Two ALS-causing mutants (TDP-43(Q331K) TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon neuron death when expressed mice at levels a cell type-selective pattern similar endogenous TDP-43. Mutant...
Misfolded proteins accumulating in several neurodegenerative diseases (including Alzheimer, Parkinson, and Huntington diseases) can cause aggregation of their native counterparts through a mechanism similar to the infectious prion protein's induction pathogenic conformation onto its cellular isoform. Evidence for such prion-like has now spread main misfolded proteins, SOD1 TDP-43, implicated amyotrophic lateral sclerosis (ALS). The major may therefore have mechanistic parallels...
Abstract TDP-43 is a primarily nuclear RNA-binding protein, whose abnormal phosphorylation and cytoplasmic aggregation characterizes affected neurons in patients with amyotrophic lateral sclerosis frontotemporal dementia. Here, we report that physiological mouse human brain forms homo-oligomers are resistant to cellular stress. Physiological oligomerization mediated by its N-terminal domain, which can adopt dynamic, solenoid-like structures, as revealed 2.1 Å crystal structure combination...
Abstract Aggregation of the RNA‐binding protein TAR DNA‐binding 43 (TDP‐43) is key neuropathological feature neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP‐43 predominantly nuclear, forms oligomers, contained in biomolecular condensates assembled by liquid–liquid phase separation (LLPS). disease, cytoplasmic or intranuclear inclusions. How transitions from to pathological states remains...
Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed TDP-43 proteinopathies
PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is only defined constituent transmissible agent causing diseases. Expression PrPC in host organism necessary for replication neurotoxicity. Understanding diseases necessitates detailed structural insights into PrPSc. Towards this goal, we have developed comprehensive collection monoclonal antibodies denoted POM1 to POM19 directed against many different epitopes mouse PrPC. Three are located within N-terminal...
The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis). Impairment this process can contribute to autoimmunity. We show that Mfge8 is identical the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8(-/-) mice, all splenic was derived from FDCs rather than TBMphis. However, TBMphis acquired displayed...
Nuclear import receptors, also called importins, mediate nuclear of proteins and chaperone aggregation-prone cargoes (e.g., neurodegeneration-linked RNA-binding [RBPs]) in the cytoplasm. Importins were identified as modulators cellular toxicity elicited by arginine-rich dipeptide repeat (DPRs), an aberrant protein species found C9orf72-linked amyotrophic lateral sclerosis (ALS) frontotemporal dementia (FTD). Mechanistically, link between importins DPRs remains unclear. Here, we show that...