A5086079816- Alzheimer's disease research and treatments
- Amino Acid Enzymes and Metabolism
- Supramolecular Self-Assembly in Materials
- Chemical Synthesis and Analysis
- Drug Transport and Resistance Mechanisms
- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Advanced Proteomics Techniques and Applications
- Pharmacological Effects and Toxicity Studies
- Neuroscience and Neuropharmacology Research
- Glycosylation and Glycoproteins Research
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Machine Learning in Bioinformatics
- Amyotrophic Lateral Sclerosis Research
- Inhalation and Respiratory Drug Delivery
- Analytical Chemistry and Chromatography
- Genetic Neurodegenerative Diseases
- thermodynamics and calorimetric analyses
- Pharmacological Receptor Mechanisms and Effects
- Diet and metabolism studies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Phosphodiesterase function and regulation
- Pharmacogenetics and Drug Metabolism
- Diabetes, Cardiovascular Risks, and Lipoproteins
Heinrich Heine University Düsseldorf
2018-2023
AC Immune (Switzerland)
2023
Forschungszentrum Jülich
2015-2021
Ludwig-Maximilians-Universität München
2018
Institute for Complex Systems
2018
Stadtwerke Jülich (Germany)
2018
Effective therapies are urgently needed to safely target TDP-43 pathology as it is closely associated with the onset and development of devastating diseases such frontotemporal lobar degeneration (FTLD-TDP) amyotrophic lateral sclerosis (ALS). In addition, present a co-pathology in other neurodegenerative Alzheimer's disease Parkinson's disease. Our approach develop TDP-43-specific immunotherapy that exploits Fc gamma-mediated removal mechanisms limit neuronal damage while maintaining...
Abstract While amyloid-β protein (Aβ) aggregation into insoluble plaques is one of the pathological hallmarks Alzheimer’s disease (AD), soluble oligomeric Aβ has been hypothesized to be responsible for synapse damage, neurodegeneration, learning, and memory deficits in AD. Here, we investigate vitro vivo efficacy d -enantiomeric peptide RD2, a rationally designed derivative previously described lead compound D3, which developed efficiently eliminate toxic Aβ42 oligomers as promising...
Targeting toxic amyloid beta (Aβ) oligomers is currently a very attractive drug development strategy for treatment of Alzheimer´s disease. Using mirror-image phage display against Aβ1-42, we have previously identified the fully D-enantiomeric peptide D3, which able to eliminate Aβ and has proven therapeutic potential in transgenic disease animal models. However, there little information on pharmacokinetic behaviour peptides general. Therefore, conducted experiments with tritium labelled...
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of dementia. Until now, there no curative therapy available. Previously, we selected amyloid-beta (Aβ) targeting peptide D3 consisting 12 d-enantiomeric amino acid residues by mirror image phage display as potential drug candidate for treatment AD. In current approach, investigated optimization linear with free C-terminus (D3COOH) chemical modifications. First, impact net charge was second, cyclization...
Amyloid-beta (Aβ) oligomers are thought to be causative for the development and progression of Alzheimer's disease (AD). Starting from Aβ oligomer eliminating d-enantiomeric peptide D3, we developed applied a two-step procedure based on microarrays identify D3 derivatives with increased binding affinity specificity monomeric Aβ(1–42) further enhance elimination efficacy. Out more than 1000 derivatives, selected seven novel d-peptides, named ANK1 ANK7, characterized them in detail vitro. All...
The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer's disease (AD). In particular, small neurotoxic Aβ oligomers are considered responsible for development and progression AD. Therefore, elimination thesis represents a potential causal therapy Starting from well-characterized d-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. underlying hypothesis ligands stabilize these species within various equilibria with assemblies, leading...
Pressure can shift the polymer-monomer equilibrium of Aβ, increasing pressure first leads to a release Aβ-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high NMR spectroscopy, differences partial molar volumes ΔV0 and compressibility factors Δβ' polymerization were determined different temperatures. The d-enantiomeric peptides RD2 RD2D3 bind monomeric Aβ with affinities substantially those for fibril formation. reducing concentration below critical...
Inhibition of the self-assembly process amyloid-beta and even more removal already existing toxic assemblies represent promising therapeutic strategies against Alzheimer's disease. To approach this aim, we selected a d-enantiomeric peptide by phage-display based on interaction with monomers. This lead compound was successfully optimized microarrays respect to its affinity specificity target resulting in d-peptides both increased hydrophobicity net charge. Here, present detailed biophysical...
Alzheimer's disease, a multifactorial incurable disorder, is mainly characterised by progressive neurodegeneration, extracellular accumulation of amyloid-β protein (Aβ), and intracellular aggregation hyperphosphorylated tau protein. During the last years, Aβ oligomers have been claimed to be disease causing agent. Consequently, development compounds that are able disrupt already existing highly desirable. We developed d-enantiomeric peptides, consisting solely amino acid residues, for direct...
Diffusible amyloid- (A) oligomers are currently presumed to be the most cytotoxic A assembly and held responsible trigger pathogenesis of Alzheimer's disease (AD).Thus, a prominent target in AD drug development.Previously, we reported on our solely D-enantiomeric peptide D3 its derivatives as candidates.Here, compare one promising derivatives, ANK6, with tandem version (tANK6), head-to-tail cyclized isoform (cANK6r).In vitro tests investigating D-peptides' potencies inhibit aggregation,...
Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, C-terminal 300 amino acids of DISC1 have been found to mediate protein-protein interactions harbor functionally phosphorylation sites disease-associated polymorphisms. However, long disordered regions oligomer-forming subdomains so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are...