A5009036426- Ubiquitin and proteasome pathways
- Alzheimer's disease research and treatments
- Glycosylation and Glycoproteins Research
- Biochemical effects in animals
- Trace Elements in Health
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Parkinson's Disease Mechanisms and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Protein Degradation and Inhibitors
- Carbohydrate Chemistry and Synthesis
- Folate and B Vitamins Research
- Prion Diseases and Protein Misfolding
- Protein Structure and Dynamics
- Molecular Sensors and Ion Detection
- Enzyme Structure and Function
- Redox biology and oxidative stress
- Iron Metabolism and Disorders
- Lysosomal Storage Disorders Research
- Supramolecular Self-Assembly in Materials
- Genetics and Neurodevelopmental Disorders
- Biomedical Research and Pathophysiology
- RNA Research and Splicing
University of Gdańsk
2014-2025
International Institute of Molecular and Cell Biology
2016-2018
University of Wrocław
2006-2008
University of Siena
2006-2008
Icahn School of Medicine at Mount Sinai
2005
Polish Academy of Sciences
1989-2004
Max Planck Institute for Brain Research
2000
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
1989
The proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, synaptic efficacy plasticity. Proteasome dysfunction is a prominent feature Alzheimer's disease (AD). We show that prevention by genetic manipulation delays mortality, cell death, cognitive deficits fly culture AD models. developed transgenic mouse with neuronal-specific overexpression that, when crossed an model, showed reduced mortality deficits. To...
Proteasomes catalyze protein degradation in cells and play an integral role cellular homeostasis. Its activity decreases with age alongside the load of defective proteins, resulting from mutations or oxidative stress-induced damage. Such proteins are prone to aggregation and, if not efficiently degraded, can form toxic oligomers amyloid plaques. Developing effective way activate proteasome could prevent such pathologies. Designing activators is easy because they do bind active site, which...
Cysteine proteases (CPs) are responsible for many biochemical processes occurring in living organisms and they have been implicated the development progression of several diseases that involve abnormal protein turnover. The activity CPs is regulated among others by their specific inhibitors: cystatins. main aim this review to discuss structure-activity relationships cysteine cystatins, as well some synthetic inhibitors structurally based on binding fragments
Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal accumulation and deposition of peptides (amyloid-β, Aβ) derived from amyloid precursor protein. Here, we present structure Zn2+ binding sites human rat Aβ(1−28) fragments in water/sodium dodecyl sulfate (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations measured after addition at T > 310 K allowed us to assign donor atoms both zinc complexes. Asp-1 amine, His-6 Nδ, Glu-11 COO-, His-13 Nε...
Proline- and arginine-rich peptide PR11 is an allosteric inhibitor of 20S proteasome. We modified its sequence inter alia by introducing HbYX, RYX, or RHbX C-terminal extensions (Hb, hydrophobic moiety; R, arginine; Y, tyrosine; X, any residue). Consequently, we were able to improve inhibitory potency convert inhibitors into strong activators: the former with aromatic penultimate Hb residue latter HbYX motif. The PR activator stimulated proteasome in vitro efficiently degrade protein...
Failures in protein homeostasis are linked to Parkinson's disease (PD) and other neurodegenerative diseases. Lewy bodies, proteinaceous inclusions rich phosphorylated alpha-synuclein a hallmark of PD. Glial cell line-derived neurotrophic factor (GDNF) can eliminate body-like mouse dopamine neurons. This study explores whether GDNF has protective effects against protofibril toxicity under proteasome inhibition by lactacystin, both vitro vivo. did not shield midbrain neurons from...
The development of age-related neurodegenerative diseases is associated with the accumulation damaged and misfolded proteins. Such proteins are eliminated from cells by proteolytic systems, mainly 20S proteasomes, whose activity declines age. Its stimulation has been recognized as a promising approach to delay onset or ameliorate symptoms disorders. Here we present peptidomimetics that very effective in stimulating proteasome biochemical assays cell culture. They stable human plasma capable...
The giant proteolytic factory called the proteasome came a long way from biochemical curio to major regulator of cellular physiology and renowned drug target within ubiquitin pathway (UPP). Thanks availability highly specific inhibitors proteasome, in less than twenty years it was possible identify transcription factors, cyclins, products oncogenes as crucial substrates for UPP. Nine passed since FDA speedily approved bortezomib, inhibitor treatment multiple myeloma. One year after its...
Aging and age-related diseases are associated with a decline in the capacity of protein turnover. Intrinsically disordered proteins, as well proteins misfolded oxidatively damaged, prone to aggregation, preferentially digested by ubiquitin-independent proteasome system (UIPS), major component which is 20S proteasome. Therefore, boosting activity constitutes promising strategy counteract decrease total during aging. One way enhance proteolytic removal unwanted appears be use peptide-based...
Stability constants and ligand donor sets of the copper(II) complexes NH2-29-56(L1)(AA30GKTKEGVLYV40GSKTKEGVVH50GVATVA56-NH2), NH2-M29-D30-56(L2) Ac-M29-D30-56(L3) fragments alpha-synuclein were determined in aqueous solution for 1 : metal-to-ligand molar ratio pH range 2.5-10.5. The tyrosine residue 39th position does not take part coordination metal ion. potentiometric spectroscopic data (UV-Vis, CD, EPR) show that acetylation amino terminal group induces significant changes properties L3...
RNArchitecture is a database that provides comprehensive description of relationships between known families structured non-coding RNAs, with focus on structural similarities. The classification hierarchical and similar to the system used in SCOP CATH databases protein structures. Its central level Family, which builds Rfam catalog gathers closely related RNAs. Consensus structures Families are described reduced secondary structure representation. Evolutionarily grouped into Superfamilies....
In this study, we have asked whether proteasome composition and function are affected in cells derived from patients suffering all types of mucopolysaccharidosis (MPS), an inherited metabolic disease caused by accumulation undegraded glycosaminoglycans (GAGs). Moreover, tested if genistein, a small molecule proposed previously as potential therapeutic agent MPS, can modulate proteasomes, which might shed new light on the molecular mechanisms action isoflavone drug for macromolecule storage...
The proteasome is a pivotal element of controlled proteolysis, responsible for the catabolic arm proteostasis. By inducing apoptosis, small molecule inhibitors peptidolytic activities are successfully utilized in treatment blood cancers. However, clinical potential activation remains relatively unexplored. In this work, we introduce short TAT peptides derived from HIV-1 Tat protein and modified with synthetic turn-stabilizing residues as agonists. Molecular docking biochemical studies point...
Human cystatin C (hCC) is a small but very intriguing protein. Produced by all nucleated cells found in almost tissues and body fluids where, at physiological conditions, plays role of potent inhibitor cysteine proteases. Biologically active hCC monomeric protein during cellular trafficking it forms dimers, transiently losing its inhibitory activity. In vitro, dimerization was observed for the mature crystallization trials, revealing that mechanism this process based on three dimensional...
Proteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results gradual accumulation misfolded/damaged proteins, leading to their aggregation. It has been postulated that activators may facilitate removal such aggregation-prone proteins and thus prevent development neurodegenerative disorders. However, the discovery pharmacologically relevant compounds is...
Earthworm coelomic fluid (CF) is known as a rich source of various bioactive compounds with promising anticancer features. However, it has been demonstrated that CF affects functionality both, cancer and normal cells. This non-selective activity causes major problem for medical application CF. In this study, we present the active protein-carbohydrate fraction (AF) isolated from thermally treated earthworm Dendrobaena veneta. The in vitro effect AF was examined human colon model including...
This work reports detailed characteristics of the antimicrobial peptide Intestinalin (P30), which is derived from LysC enzyme Clostridium intestinale strain URNW. The shows a broader antibacterial spectrum than parental enzyme, showing potent activity against clinical strains Gram-positive staphylococci and Gram-negative pathogens causing between 3.04 ± 0.12 log kill for Pseudomonas aeruginosa PAO1 7.10 0.05 multidrug-resistant Acinetobacter baumannii KPD 581 at 5 μM concentration. Moreover,...
The homeostasis of metal ions, especially copper and zinc, is a major factor that may influence the prion diseases biological function protein (PrP). His-rich regions are basic sites for binding antioxidant activity PrP structures. Animal prion-like proteins contain also domains, their coordination chemistry provide better insight into biology structures related diseases. Herein, we report an equilibrium study on heteronuclear Zn2+−Cu2+ complexes with zrel-PrP fragments from zebrafish....
Proteasome, consisting of a tube-shaped proteolytic core particle and attached to it regulatory modules, is multifunctional enzymatic complex essential for the ubiquitin-proteasome metabolic pathway. Due its immense involvement in regulation cellular physiology, proteasome an acknowledged anticancer drug target potential treat inflammatory or degenerative diseases. So far, competitive inhibitors gain most consideration as drugs. We postulate that noncompetitively-acting small-molecule...
The stability constants, stoichiometry, and solution structures of copper(II) complexes neuropeptide gamma (NPG) (D1-A-G-H4-G-Q-I-S-H9-K-R-H12-K-T-D-S–F-V-G-L-M21-NH2) acethyl–neuropeptide (Ac–D1-A-G-H4-G-Q-I-S-H9-K-R-H12-K-T-D-S-F-V-G-L-M21-NH2) were determined in aqueous solution. For both peptides the additional deprotonations observed; therefore, potentiometric data calculations for NPG only made 2.5–7.4 pH range. Ac–NPG one deprotonation was observed, likely hydroxy group Ser residue,...