A5073944069- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- Extracellular vesicles in disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Nuclear reactor physics and engineering
- Nuclear Physics and Applications
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Galectins and Cancer Biology
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Carbohydrate Chemistry and Synthesis
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Connective tissue disorders research
- Inflammasome and immune disorders
- Corneal Surgery and Treatments
- Nuclear Receptors and Signaling
- Signaling Pathways in Disease
Friedrich-Alexander-Universität Erlangen-Nürnberg
2021-2025
European Spallation Source
2018-2024
University of Stuttgart
2020-2024
Kiel University
2014-2023
MSH Medical School Hamburg – University of Applied Sciences and Medical University
2020
Johannes Gutenberg University Mainz
2011-2018
Ludwig-Maximilians-Universität München
2017
University Hospital Magdeburg
2017
Tambov State Technical University
2017
Munich University of Applied Sciences
2017
Abstract To date, no reliable clinically applicable biomarker has been established for Parkinson’s disease. Our results indicate that a long anticipated blood test disease may be realized. Following the isolation of neuron-derived extracellular vesicles patients and non-Parkinson’s individuals, immunoblot analyses were performed to detect vesicle-derived α-synuclein. Pathological α-synuclein forms derived from neuronal could detected under native conditions significantly increased in all...
Type I fibrillar collagen is the most abundant protein in human body, crucial for formation and strength of bones, skin, tendon. Proteolytic enzymes are essential initiation assembly fibrils by cleaving off propeptides. We report that Mep1a −/− Mep1b mice revealed lower amounts mature compared with WT exhibited significantly reduced deposition along markedly decreased tissue tensile strength. While exploring mechanism this phenotype, we found cleavage full-length procollagen heterotrimers...
SARS-CoV-2, the virus causing COVID-19 pandemic, changes frequently through appearance of mutations constantly leading to new variants. However, only few variants evolve as dominating and will be considered "Variants Concern" (VOCs) by world health organization (WHO). At end 2020 alpha (B.1.1.7) variant appeared in United Kingdom dominated pandemic situation until mid 2021 when it was substituted delta (B.1.617.2) that first India predominant. 2021, SARS-CoV-2 omicron (B.1.1.529) evolved...
Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R), but therapeutic success limited. EGF-R stimulated by soluble ligands, which are derived from transmembrane precursors ADAM17-mediated proteolytic cleavage. In mouse intestinal models in the absence of ADAM17, tumorigenesis was almost completely inhibited, and few remaining tumors were low-grade dysplasia. RNA sequencing analysis demonstrated down-regulation STAT3 Wnt pathway components. Because on...
Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggests involvement autophagy as well lysosomal deficiencies. Because CTSD (cathepsin D) has been proposed to be major protease involved in degradation, its deficiency linked presence insoluble conformers brain mice and humans transcellular transmission aggregates....
Abstract Biallelic loss of SPG11 function constitutes the most frequent cause complicated autosomal recessive hereditary spastic paraplegia (HSP) with thin corpus callosum, resulting in progressive multisystem neurodegeneration. While impact neuroinflammation is an emerging and potentially treatable aspect neurodegenerative diseases leukodystrophies, role immune cells SPG11–HSP patients unknown. Here, we performed a comprehensive immunological characterization SPG11–HSP, including...
Significance Apart from the lysosomal integral membrane protein type-2 (LIMP-2)–dependent trafficking of β-glucocerebrosidase (GC) to lysosomes, little is known about interaction LIMP-2 and GC on molecular level. The structural biochemical characterization LIMP-2/GC sites has potential importance for design GC-activating compounds. We show that a LIMP-2–derived helical peptide can be used efficient purification activation recombinant endogenous GC. These results provide framework activators...
Abstract Soluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R generated proteolytically from its membrane bound form A Disintegrin And Metalloprotease (ADAM) 10 17 were shown to perform ectodomain shedding of the in vitro vivo . However, under certain conditions not all could be assigned ADAM10/17 activity. Here, we...
Article23 September 2019Open Access Source DataTransparent process Prdx4 limits caspase-1 activation and restricts inflammasome-mediated signaling by extracellular vesicles Simone Lipinski Corresponding Author [email protected] orcid.org/0000-0002-9322-7372 Institute of Clinical Molecular Biology, Christian-Albrechts-University University Hospital Schleswig-Holstein, Campus Kiel, Germany Search for more papers this author Steffen Pfeuffer Philipp Arnold Anatomical Institute, Christian Treitz...
The B.1.1.7 variant of the SARS-CoV-2 virus shows enhanced infectiousness over wild type virus, leading to increasing patient numbers in affected areas. Amino acid exchanges within spike protein affect inter-monomeric contact sites trimer (A570D and D614G) as well ACE2-receptor interface region (N501Y), which comprises receptor-binding domain (RBD) protein. However, molecular consequences mutations on dynamics stability or ACE2 binding are largely unknown. Here, simulations comparing with...
Cathepsin D (CTSD) is a lysosomal protease important for the degradation of various substrates, including disease-associated proteins like α-synuclein (a-syn), amyloid precursor protein (APP) and tau, all which tend to aggregate if not efficiently degraded. Hence, it surprising that genetic variants within CTSD gene have been linked neurodegenerative diseases, Parkinson’s Alzheimer’s disease (PD, AD), as well storage disorder neuronal ceroid lipofuscinosis type-10 (NCL10). Although recent...
Genetic variants in the DNA methyltransferase 3 A (DNMT3A) locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of epigenetic machinery physiologically involved methylation. We show that plays a critical role maintaining intestinal homeostasis and gut barrier function. expression downregulated epithelial cells from IBD patients upon tumor necrosis factor treatment murine organoids. Ablation Caco-2 results global hypomethylation, which linked to impaired...
Extracellular Vesicles (EVs) play a crucial role in cell differentiation. Despite its as well-established vertebrate model, little is known about EVs during zebrafish embryogenesis. This study investigates embryogenesis, analysing size- and concentration-changes over time.Wild-type AB strain larvae (zfl) were collected at 24, 48, 72, 96 h post fertilization (hpf) homogenized. isolated characterized using flow cytometry, negative staining transmission electron microscopy (TEM), nanoparticle...
During perinatal development, liver metabolism is tightly regulated to ensure energy supply for the newborn. Before birth, glycogen stored in hepatocytes and later metabolized glucose, meeting demands of neonate. Shortly after lipogenesis begins, driven by transcriptional activation enzymes involved fatty acid oxidation. These processes are thought be largely systemic insulin glucagon levels. However, role liver-derived local factors neonatal hepatocyte remains unexplored. Kupffer cells...
An altered gut microbiota, particularly the expansion of Prevotellaceae members, is increasingly implicated in pathogenesis rheumatoid arthritis (RA), yet mechanisms hind this phenomenon remain unclear. Here, we demonstrate that Palleniella intestinalis, a member family, induces 100% incidence genetically resistant C57BL/6 mice. Inoculation with P. intestinalis modifies microbiota ecology, increases intestinal permeability, and selectively activates colonic CD11b⁺CD11c⁺ myeloid cells,...
Abstract Targeting proteins to their final cellular destination requires transport mechanisms and nearly all lysosomal enzymes reach the lysosome via mannose-6-phosphate receptor pathway. One of few known exceptions is enzyme β-glucocerebrosidase (GCase) that integral membrane protein type-2 (LIMP-2) as a proprietary transporter. Genetic variations in GCase encoding gene GBA1 cause Gaucher’s disease (GD) present highest genetic risk factor develop Parkinson’s (PD). Activators targeting...
Glioblastoma (GBM) is a typically lethal type of brain tumor with median survival 15 months postdiagnosis. This negative prognosis prompted the exploration alternative treatment options. In particular, reliance GBM on angiogenesis triggered development anti-VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab. Although its application in human only increased progression-free periods but did not improve overall survival, physicians and researchers still utilize...
Solvent-induced fibrillar aggregates of beta-lactoglobulin occur only in a certain balance between hydrophobic forces and electrostatic interactions. We hypothesize, that different solvent molecules as well rising temperatures influence this equilibrium thus the optimum to produce amyloid aggregates. Dimethyl sulfoxide (DMSO), methanol ethanol all resulted polydisperse solutions with worm-like spherical-aggregates, albeit degrees: volume fraction required for aggregation was DMSO (50%) >...
Background & AimsThroughout life, the intestinal epithelium undergoes constant self-renewal from stem cells. Together with genotoxic stressors and failing DNA repair, this causes susceptibility toward malignant transformation. X-box binding protein 1 (XBP1) is a stress sensor involved in unfolded response (UPR). We hypothesized that XBP1 acts as signaling hub to regulate epithelial damage responses.MethodsData The Cancer Genome Atlas were analyzed for association of colorectal cancer (CRC)...