A5089353861- Phosphodiesterase function and regulation
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Neurological diseases and metabolism
- Trace Elements in Health
- Renin-Angiotensin System Studies
- Tryptophan and brain disorders
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- 14-3-3 protein interactions
- RNA regulation and disease
- Amino Acid Enzymes and Metabolism
- Computational Drug Discovery Methods
- Genetics and Neurodevelopmental Disorders
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Neuroendocrine regulation and behavior
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Infectious Encephalopathies and Encephalitis
- Influenza Virus Research Studies
- Signaling Pathways in Disease
Heinrich Heine University Düsseldorf
2016-2025
National Agricultural Library
2018-2023
Walter de Gruyter (Germany)
2018-2023
Düsseldorf University Hospital
2020-2022
Baidu (China)
2018
Hochschule Düsseldorf University of Applied Sciences
2012-2014
University of California, San Francisco
1999-2012
Institute for Neurodegenerative Disorders
2008-2012
Friedrich-Loeffler-Institut
2008
Centre National de la Recherche Scientifique
2006
Prion diseases in humans and animals are invariably fatal. Prions composed of a disease-causing isoform (PrP(Sc)) the normal host prion protein (PrP(C)) replicate by stimulating conversion PrP(C) into nascent PrP(Sc). We report here that tricyclic derivatives acridine phenothiazine exhibit half-maximal inhibition PrP(Sc) formation at effective concentrations (EC(50)) between 0.3 microM 3 cultured cells chronically infected with prions. The EC(50) for chlorpromazine was microM, whereas...
Article23 September 2020Open Access Transparent process SARS-CoV-2 targets neurons of 3D human brain organoids Anand Ramani orcid.org/0000-0002-2380-8649 Institute Human Genetics, University Hospital Düsseldorf, Heinrich-Heine-Universität, Germany Search for more papers by this author Lisa Müller orcid.org/0000-0002-0728-0012 Virology, Medical Faculty, Philipp N Ostermann Elke Gabriel Pranty Abida-Islam Andreas Müller-Schiffmann Neuropathology, Aruljothi Mariappan...
According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor–related protein-1 (LRP1) in brain capillaries blood-brain barrier (BBB) contributes neurotoxic amyloid-β (Aβ) accumulation and drives Alzheimer's disease (AD) pathology. However, due conflicting reports on involvement LRP1 Aβ transport expression endothelium, role at BBB is uncertain. As global Lrp1 deletion mice lethal, appropriate models study function are lacking. Moreover, relevance systemic...
The role of the central nervous system in host response to infection and inflammation modulation these responses by hypothalamic-pituitary-adrenal are well established. In animals, activation defense mechanisms increases non-rapid eye movement (NREM) sleep amount intensity, which, turn, thought support defense, or body's ability defend itself against challenges its immune system. humans, evidence is conflicting. Therefore, we investigated effects three placebo-controlled doses endotoxin on...
The cellular prion protein of the mouse, m PrP C , consists 208 amino acids (residues 23–231). It contains a carboxy‐terminal domain, PrP(121–231), which represents an autonomous folding unit with three α‐helices and two‐stranded antiparallel β‐sheet. We expressed complete acid sequence protein, PrP(23–231), in cytoplasm Escherichia coli . PrP(23–231) was solubilized from inclusion bodies by 8 M urea, oxidatively refolded purified to homogeneity conventional chromatographic techniques....
Significance Synucleinopathies such as Parkinson’s disease feature deposition of misfolded α-synuclein. It is likely that cellular proteostasis compensates for α-synuclein to some extent, but, once exhausted, can form seeds a prion-like spread in the brain. Here, we demonstrate that, human dopaminergic neurons and mouse brain, H1N1 influenza virus induces aggregation by blocking protein degradation pathways. Following intranasal instillation, spreading along olfactory route into brain areas...
The DISC1 protein is implicated in major mental illnesses including schizophrenia, depression, bipolar disorder, and autism. Aberrant mitochondrial dynamics are also associated with illness. plays a role transport neuronal axons, but its effects dendrites have yet to be studied. Further, the mechanisms of this regulation development brain function poorly understood. Here we demonstrated that couples fusion machinery via interaction outer membrane GTPase proteins Miro1 Miro2, TRAK1 TRAK2...
Transgenic (Tg) mouse lines that express chimeric mouse-human prion protein (PrP), designated MHu2M, are susceptible to prions from patients with sporadic Creutzfeldt-Jakob disease (sCJD). With the aim of decreasing incubation time fewer than 200 days, we constructed transgenes in which one or more nine human residues MHu2M were changed mouse. The construct murine at positions 165 and 167 was expressed Tg(MHu2M,M165V,E167Q) mice resulted shortening approximately 110 days for sCJD patients. a...
Disrupted-in-schizophrenia 1 (DISC1) and other genes have been identified recently as potential molecular players in chronic psychiatric diseases such affective disorders schizophrenia. A mechanism of how these may be linked to the majority sporadic cases remains unclear. The nature irreversibility clinical symptoms a subgroup prompted us investigate whether proteins corresponding candidate displayed subtle features protein aggregation. Here, we show that postmortem brain samples distinct...
Prion diseases are caused by conversion of a normally folded, non-pathogenic isoform the prion protein (PrP(C)) to misfolded, pathogenic (PrP(Sc)). inoculation experiments in mice expressing homologous PrP(C) molecules on different genetic backgrounds displayed incubation times, indicating that reaction may be influenced other gene products. To identify genes contribute pathogenesis, we analysed times prions which product was inactivated, knocked out or overexpressed. We tested 20 candidate...
Several lines of evidence suggest that the amyloid-β-peptide (Aβ) plays a central role in pathogenesis Alzheimer's disease (AD). Not only Aβ fibrils but also small soluble oligomers particular are suspected to be major toxic species responsible for development and progression. The present study reports on vitro vivo properties targeting d-enantiomeric amino acid peptide D3. We show next plaque load inflammation reduction, oral application improved cognitive performance AD transgenic mice. In...
Neuregulin-1 (NRG1) and Disrupted-in-Schizophrenia-1 (DISC1) are promising susceptibility factors for schizophrenia. Both multifunctional proteins with roles in a variety of neurodevelopmental processes, including progenitor cell proliferation, migration, differentiation. Here, we provide evidence linking these together single pathway, which is mediated by ErbB receptors PI3K/Akt. We show that signaling NRG1 NRG2, but not NRG3, increase expression an isoform DISC1 vitro. Receptors ErbB2...
Disrupted-in-schizophrenia 1 (DISC1) is a mental illness gene first identified in Scottish pedigree. So far, DISC1-dependent phenotypes animal models have been confined to expressing mutant DISC1. Here we investigated how pathology of full-length DISC1 protein could be major mechanism sporadic illness. We demonstrate that novel transgenic rat model, modestly overexpressing the transgene, showed consistent with significant role misassembly The tgDISC1 displayed mainly perinuclear aggregates...
Abstract Despite amyloid plaques, consisting of insoluble, aggregated amyloid-β peptides, being a defining feature Alzheimer’s disease, their significance has been challenged due to controversial findings regarding the correlation cognitive impairment in disease with plaque load. The cascade hypothesis defines soluble oligomers, multiple monomers, as precursors insoluble plaques. Dissecting biological effects single for example dimers, an abundant oligomer associated clinical progression...
Mammalian prions refold host glycosylphosphatidylinositol-anchored PrPC into β-sheet–rich PrPSc. PrPSc is rapidly truncated a C-terminal PrP27-30 core that stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, subcellular locations are poorly understood; live prion visualization has not previously been achieved. A key obstacle the inaccessibility epitopes. We overcame this hurdle by focusing on nascent full-length rather than its...
Abstract Prion diseases are invariably fatal, neurodegenerative transmitted by an infectious agent, PrP Sc , a pathogenic, conformational isoform of the normal prion protein (PrP C ). Heterocyclic compounds such as acridine derivatives like quinacrine abolish infectivity in cell culture model disease. Here, we report that these execute their antiprion activity redistributing cholesterol from plasma membrane to intracellular compartments, thereby destabilizing domains. Our findings supported...
Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to progressive brain conditions, persistent functional disturbances neurons would result in disturbed proteostasis the brains schizophrenia patients, leading increased abundance specific misfolded, insoluble proteins. Identification such proteins facilitate elucidation molecular processes underlying these devastating conditions. therefore generated antibodies against pooled proteome...