A5029952472- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Supramolecular Self-Assembly in Materials
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- History and advancements in chemistry
- Chemical Synthesis and Analysis
- HIV Research and Treatment
- Advanced Chemical Physics Studies
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Glycosylation and Glycoproteins Research
- biodegradable polymer synthesis and properties
- Genomics and Rare Diseases
- Click Chemistry and Applications
- Peptidase Inhibition and Analysis
- S100 Proteins and Annexins
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Various Chemistry Research Topics
- Ubiquitin and proteasome pathways
- Molecular spectroscopy and chirality
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
Friedrich-Alexander-Universität Erlangen-Nürnberg
2015-2024
University of Zurich
2021-2024
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...
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...
PurposeMicrocephaly is a sign of many genetic conditions but has been rarely systematically evaluated. We therefore comprehensively studied the clinical and landscape an unselected cohort patients with microcephaly.MethodsWe performed assessment, high-resolution chromosomal microarray analysis, exome sequencing, functional studies in 62 (58% primary microcephaly [PM], 27% secondary [SM], 15% unknown onset).ResultsWe found severity developmental delay/intellectual disability correlating PM,...
Amyloid-[Formula: see text] (A[Formula: text]) oligomers play a crucial role in Alzheimer's disease due to their neurotoxic aggregation properties. Fibrillar A[Formula: oligomerization can lead protofilaments and protofilament pairs via oligomer elongation association, respectively. Small fibrillar adopt the topology, whereas fibrils contain at least pairs. To date, underlying growth mechanism from mature fibril still remains be elucidated. Here, we performed all-atom molecular dynamics...
A β-sheet-binding scaffold was equipped with long-range chemical groups for tertiary contacts toward specific regions of the Alzheimer's Aβ fibril. The new constructs contain a trimeric aminopyrazole carboxylic acid, elongated C-terminal binding site, whose influence on aggregation behavior Aβ42 peptide studied. MD simulations after trimer docking to anchor point (F19/F20) suggest distinct complex structures each which featured additional interactions characteristic regions. Members group...
Alzheimer's disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder that mainly affects older adults. One pathological hallmarks AD abnormally aggregated Tau protein forms fibrillar deposits in brain. In AD, pathology correlates strongly with clinical symptoms, cognitive dysfunction, and neuronal death.We aimed to develop novel therapeutic D-amino acid peptides as fibrillization inhibitors. It has been previously demonstrated are protease stable less...
Anoctamins are a family of Ca
The nuclear lamina lines the inner membrane providing a structural framework for nucleus. Cellular processes, such as envelope breakdown during mitosis or export of large ribonucleoprotein complexes, are functionally linked to disassembly lamina. In general, is mediated by phosphorylation, but precise molecular mechanism still not completely understood. Recently, we suggested novel egress herpesviral capsids which involves cellular isomerase Pin1. this study, focused on mechanistic details...
A variety of neurodegenerative disorders, including Alzheimer disease (AD), are associated with neurofibrillary tangles composed the tau protein, as well toxic oligomers. Inhibitors pathological aggregation, interrupting self-assembly, might be useful for development therapeutics. Employing mirror image phage display a large peptide library (over 109 different peptides), we have identified fibril binding peptides consisting d-enantiomeric amino acids. extremely protease stable and not or...
Recent experimental data demonstrate that small, soluble amyloid-beta42 oligomers play an important role in Alzheimer's disease because they exhibit neurotoxic properties and also act as seed for fibril growth. We performed all-atom molecular dynamics simulations explicit solvent of 0.7 micros total on five Abeta9-42 (monomer through pentamer) starting from the conformation. The initial conformation proves to be stable trimer pentamer, two parallel in-register beta-sheets well connecting...
More than the sum of its parts: Novel hybrid compounds consisting an organic β-sheet-breaking moiety and a signaling, D-enantiomeric Aβ-recognizing peptide have been designed (see picture). The compounds, which were chemically synthesized characterized by several techniques, combine rational design drug selection from libraries inhibit Aβ oligomerization Aβ-induced synaptic pathology. Detailed facts importance to specialist readers are published as "Supporting Information". Such documents...
A key player in Alzheimer's disease is the peptide amyloid-beta (Aβ), whose aggregation into small soluble oligomers, protofilaments, and fibrils finally leads to plaque deposits human brains. The behavior of Aβ strongly modulated by nature composition peptide's environment its primary sequence properties. N-terminal residues play an important role, because they are known change propensity. Since these for first time completely resolved at molecular level a three-fold symmetric fibril...
Abstract Alzheimer's disease and other Tauopathies are associated with neurofibrillary tangles composed of Tau protein, as well toxic oligomers. Therefore, inhibitors pathological aggregation potentially useful candidates for future therapies targeting Tauopathies. Two hexapeptides within Tau, designated PHF6* (275‐VQIINK‐280) PHF6 (306‐VQIVYK‐311), known to promote aggregation. Recently, the segment has been described more potent driver We therefore employed mirror‐image phage display a...
Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing automated structural assessment missense variants on series 88 patients correlated genetic, angiographic clinical (stroke burden)...
Aβ oligomers play a key role in the pathophysiology of Alzheimer's disease. Research into structure-function relationships has been hampered by lack large amounts homogeneous and stable material. Using computational chemistry, we designed conservative cysteine substitutions aiming at accelerating stabilizing assembly dimers an intermolecular disulfide bond without changing its folding. Molecular dynamics simulations suggested that mutants AβS8C AβM35C exhibited structural properties similar...