A5006852686- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Enzyme Structure and Function
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Epigenetics and DNA Methylation
- Redox biology and oxidative stress
- Migraine and Headache Studies
- Genetics, Aging, and Longevity in Model Organisms
- Parasites and Host Interactions
- Epilepsy research and treatment
- RNA and protein synthesis mechanisms
- Genomics and Chromatin Dynamics
- Escherichia coli research studies
- Restless Legs Syndrome Research
- Neurological and metabolic disorders
- Synthesis and Reactivity of Heterocycles
- Cardiovascular Syncope and Autonomic Disorders
- Genomics, phytochemicals, and oxidative stress
- Blood disorders and treatments
- Child Abuse and Related Trauma
- Sulfur Compounds in Biology
- Pain Management and Placebo Effect
- Biochemical Analysis and Sensing Techniques
- Glutathione Transferases and Polymorphisms
University of Cologne
1989-2024
University of Michigan
2019-2023
Heidelberg University
2017-2019
Michigan United
2019
Friedrich-Alexander-Universität Erlangen-Nürnberg
2005-2009
This paper describes the development of a class peptide-based inhibitors as novel antitrypanosomal and antimalarial agents. The are based on characteristic peptide sequence for inhibition cysteine proteases rhodesain Trypanosoma brucei rhodesiense falcipain-2 Plasmodium falciparum. We exploited reactivity unsaturated electrophilic functions such vinyl-sulfones, -ketones, -esters, -nitriles. Michael acceptors inhibited both falcipain-2, at nanomolar micromolar levels, respectively. In...
To investigate if the effectiveness of a 96-hour multidisciplinary headache treatment program exceeds 20-hour and primary care.When dealing with chronic back pain, low-intensity yields no significantly better results than standard care monodisciplinary therapy; however, high-intensity does. For treatment, such comparisons are not yet available. In previous study undertaken by our Pain Center, outcome minimal intervention model (20-hour) did exceed care.Forty-two patients suffering from...
Hypothiocyanite and hypothiocyanous acid (OSCN
Trypanosoma brucei glutaredoxin 2 (Grx2) is a dithiol that specifically located in the mitochondrial intermembrane space. Bloodstream form parasites lacking Grx2 or both, and cytosolic Grx1, are viable vitro infectious to mice suggesting neither oxidoreductase needed for survival infectivity mammals. A 37 °C 39 shift changes cellular redox milieu of bloodstream cells more oxidizing conditions induces significantly stronger growth arrest wildtype compared mutant cells. Grx2-deficient...
Most known thioredoxin-type proteins (Trx) participate in redox pathways, using two highly conserved cysteine residues to catalyze thiol-disulfide exchange reactions. Here we demonstrate that the so far unexplored Trx2 from African trypanosomes (Trypanosoma brucei) lacks protein disulfide reductase activity but functions as an effective temperature-activated and redox-regulated chaperone. Immunofluorescence microscopy fractionated cell lysis revealed is located mitochondrion of parasite....
Proteostasis and redox homeostasis are tightly interconnected most protein quality control pathways under direct regulation which allow cells to immediately respond oxidative stress conditions. The activation of ATP-independent chaperones serves as a first line defense counteract unfolding aggregation proteins. Conserved cysteine residues evolved redox-sensitive switches upon reversible oxidation induce substantial conformational rearrangements the formation chaperone-active complexes. In...
Trypanosomatids have a unique trypanothione-based thiol redox metabolism. The parasite-specific dithiol is synthesized from glutathione and spermidine, with glutathionylspermidine as intermediate catalyzed by trypanothione synthetase. In this study, we address the oxidative stress response of African trypanosomes special focus on putative protein S-thiolation.Challenging bloodstream Trypanosoma brucei diamide, H2O2 or hypochlorite results in distinct levels reversible overall S-thiolation....
The bacterial pathogen Mycobacterium tuberculosis is the leading cause of death by an infectious disease among humans. Here, we describe a previously uncharacterized M. protein, Rv0991c, as molecular chaperone that activated oxidation. Rv0991c has homologs in most lineages and appears to function analogously well-characterized Escherichia coli redox-regulated Hsp33, despite dissimilar protein sequence. transcriptionally coregulated with hsp60 hsp70 genes tuberculosis, suggesting functions...
ABSTRACT Oxidative stress represents a major challenge for cellular proteostasis. The accumulation of reactive oxygen species, such as hydrogen peroxide, impairs the fidelity protein biosynthesis and causes non-specific oxidative modifications aggregation. This situation is further aggravated by stress-mediated drop in ATP levels, which reduces activity ATP-dependent chaperones proteases. We now demonstrate that to cope with unfolding stress, human cells rely on moonlighting function TRC40,...
The mitochondrial disulphide relay machinery is essential for the import and oxidative folding of many proteins in intermembrane space. Its core component, receptor MIA40 (also CHCHD4), serves as an oxidoreductase but also a chaperone holdase, which initially interacts with its substrates non‐covalently before introducing bonds retaining Interactome studies have identified diverse MIA40, among them intrinsically disordered HCLS1‐associated protein X‐1 (HAX1). Interestingly, this does not...
Summary A central aspect of aging research concerns the question as to when individuality in lifespan arises and what mechanism(s) promote potentially manifest individual differences longevity. We have now discovered that a transient increase reactive oxygen species (ROS), which occurs naturally during early development subpopulation synchronized Caenorhabditis elegans , sets processes into motion stress resistance, improve redox homeostasis ultimately prolong those animals. find these...
Multimodale Therapieprogramme für Patienten mit chronischen Kopfschmerzen umfassen neben der medikamentösen Optimierung Verhaltenstherapien wie z. B. Entspannungsverfahren, Biofeedback, kognitive Stressbewältigung. Erfolgreich sind eng aufeinander abgestimmte Behandlungen, bei denen Therapeuten und Patient ein gemeinsames Schmerzmodell Therapieziel haben. Ziele u. a. die Veränderung dysfunktionaler Denk- Verhaltensmuster eine verbesserte Selbstwirksamkeit Kompetenzerleben. Wichtig ist es,...