A5001823180- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Protein Structure and Dynamics
- Trace Elements in Health
- S100 Proteins and Annexins
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Ubiquitin and proteasome pathways
- Hydrocarbon exploration and reservoir analysis
- Microtubule and mitosis dynamics
- Ginkgo biloba and Cashew Applications
- Cellular transport and secretion
- Metabolism and Genetic Disorders
- Neurological disorders and treatments
- Drug Transport and Resistance Mechanisms
- Methane Hydrates and Related Phenomena
- Geochemistry and Geologic Mapping
- Lysosomal Storage Disorders Research
- Neonatal Respiratory Health Research
- Catalytic Processes in Materials Science
- Mitochondrial Function and Pathology
- Neonatal Health and Biochemistry
- Genomics and Chromatin Dynamics
- Magnetic and Electromagnetic Effects
- Connexins and lens biology
Chalmers University of Technology
2016-2025
Umeå University
2012-2023
University of Szeged
1986-2019
Hungarian Academy of Sciences
1999-2015
Eötvös Loránd University
2003-2015
Von Karman Institute for Fluid Dynamics
2008-2012
Mining and Geological Survey of Hungary
2009
Institute of Molecular Life Sciences
2003-2007
Johnson University
2001-2006
University of California, San Francisco
2006
Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated neurodegenerative diseases. While genetic environmental factors influence amyloid formation, molecular triggers and/or facilitators not well defined. Growing evidence suggests that non-identical proteins may accelerate reciprocal aggregation in prion-like fashion. humans encode ~30 amyloidogenic proteins, the gut microbiome also produces...
Significance Protein assembly into ordered so-called amyloid fibers is a process that promotes several neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease (PD). Also type-2 diabetes (T2D) involving formation, although it occurs in the pancreas. Since protein forms amyloids PD, α-synuclein (aS), also expressed pancreas, we investigated whether could affect aggregation of peptide involved T2D, vice versa. Using vitro methods purified proteins, here demonstrate two proteins...
The disordered tubulin polymerization promoting protein (TPPP/p25) was found to be co-enriched in neuronal and glial inclusions with α-synuclein Parkinson disease multiple system atrophy, respectively; however, co-occurrence of β-amyloid (Aβ) human brain has been recently reported, suggesting the existence mixed type pathologies that could result obstacles correct diagnosis treatment. Here we identified TPPP/p25 as an interacting partner soluble Aβ oligomers major risk factors for Alzheimer...
The protein mediator of ERBB2-driven cell motility 1 (Memo1) is connected to many signaling pathways that play key roles in cancer. Memo1 was recently postulated bind copper (Cu) ions and thereby promote the generation reactive oxygen species (ROS) cancer cells. Since concentration Cu as well ROS are increased cells, both can be toxic if not regulated. Here, we investigated Cu-binding capacity using an array biophysical methods at reducing oxidizing conditions vitro. We find coordinates two...
Amyloid fibrils are protein polymers noncovalently assembled through β-strands arranged in a cross-β structure. Biological amyloids were considered chemically inert until we and others recently demonstrated their ability to catalyze chemical reactions vitro. To further explore the functional repertoire of amyloids, here probe if α-synuclein (αS) display reactivity toward DNA. We demonstrate that αS bind DNA at micromolar concentrations Using activity repair enzymes as proxy for damage,...
TPPP/p25 (tubulin polymerization-promoting protein/p25) is an unstructured protein that induces microtubule polymerization in vitro and aligned along the network transfected mammalian cells. In normal human brain, expressed predominantly oligodendrocytes, where its expression proved to be crucial for their differentiation process. Here we demonstrated of HeLa cells, doxycycline-inducible CHO10 oligodendrocyte CG-4 cells promoted acetylation alpha-tubulin at residue Lys-40, whereas...
Small organic molecules that inhibit functional bacterial amyloid fibers, curli, are promising new antibiotics. Here we investigated the mechanism by which ring-fused 2-pyridone FN075 inhibits fibrillation of curli protein CsgA. Using a variety biophysical techniques, found promotes CsgA to form off-pathway, non-amyloidogenic oligomeric species. In light generic properties amyloids, tested whether would also affect reaction human α-synuclein, an amyloid-forming involved in Parkinson's...
Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels pro-inflammatory factors in PD brain tissues. The mediator and highly amyloidogenic protein S100A9 involved the amyloid-neuroinflammatory cascade Alzheimer's disease. This first report on co-aggregation α-synuclein (α-syn) both vitro ex vivo brain. Single sequential immunohistochemistry, immunofluorescence, scanning electron atomic force (AFM) microscopies were used to...
The crowdedness of living cells, hundreds milligrams per milliliter macromolecules, may affect protein folding, function, and misfolding. Still, such processes are most often studied in dilute solutions vitro. To assess consequences the vivo milieu, we here investigated effects macromolecular crowding on amyloid fiber formation reaction α-synuclein, amyloidogenic Parkinson's disease. For this, performed spectroscopic experiments probing individual steps as a function agent Ficoll70, which is...
Amyloid fibers of the protein α-synuclein, found in Lewy body deposits, are hallmarks Parkinson's disease. We here show that α-synuclein amyloids catalyze biologically relevant chemical reactions vitro. fibers, but not monomers, catalyzed hydrolysis model ester para-nitrophenyl acetate and dephosphorylation phosphoester para-nitrophenyl-orthophosphate. When His50 was replaced with Ala esterase activity diminished. Truncation protein's C-terminus had no effect on fiber catalytic efficiency....
Recently, we isolated from bovine brain a protein, TPPP/p25 and identified as p25, brain-specific protein that induced aberrant tubulin assemblies. The primary sequence of this differs other proteins so far; however, it shows high homology with p25-like hypothetical sought via blast . Here, characterized the binding to by means surface plasmon resonance; kinetic parameters are follows: k on , 2.4 × 10 4 M –1 ·s ; off 5.4 –3 s K d 2.3 –7 M. This at substoichometric concentration promotes...
TPPP/p25 is a brain-specific protein, which induces tubulin polymerization and microtubule (MT) bundling enriched in Lewy bodies characteristic of Parkinson's disease [Tirián et al. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13976−13981]. We identified two human gene sequences, CG1−38 p25β, encoded homologous proteins, that we termed p20 p18, respectively. These proteins display 60% identity with promoting protein/p25 (TPPP/p25); however, the N-terminal segment missing. They could be...
Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such Aβ(1-42) tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), due to Alzheimer's disease (MCI-AD), (AD), vascular (VaD) patients. ELISA, dot-blotting, electrochemical impedance spectroscopy used research methods. The levels correlated each other:...
Abstract Pro-inflammatory and amyloidogenic S100A9 protein is an important contributor to Alzheimer’s disease (AD) pathology. Traumatic brain injury (TBI) viewed as a precursor state for AD. Here we have shown that S100A9-driven amyloid-neuroinflammatory cascade was initiated in TBI may serve mechanistic link between By analyzing the AD human tissues, demonstrated post-TBI tissues S100A9, produced by neurons microglia, becomes drastically abundant compared Aβ contributes both...
Animals store elastic energy in leg and foot tendons during locomotion. In the turkey, much of locomotive force generated by gastrocnemius muscle is stored as tendon deformation. Little storage occurs within muscle. During growth some avians, including mineralize portions distal to attached show increased tensile strength modulus a result. The purpose this study test hypothesis that degree mineralizing turkey directly related mineral content. To hypothesis, stress−strain behavior was...
Hydration largely determines solubility, aggregation of proteins and influences interactions between drug molecules. Despite the importance hydration, structural determination hydration structure protein surfaces is still challenging from both experimental theoretical viewpoints. The precision measurements often affected by fluctuations mobility water molecules resulting in uncertain assignment positions.Our method can utilize as an information source for prediction structure. necessary be...
Interfacial hydration strongly influences interactions between biomolecules. For example, drug–target complexes are often stabilized by networks formed hydrophilic residues and water molecules at the interface. Exhaustive exploration of is challenging for experimental as well theoretical methods due to high mobility participating molecules. In present study, we introduced a tool determination complete, void-free structures molecular interfaces. The was applied 31 including histone proteins,...
Extracellular vesicles (EVs) are small released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of deposits found in pancreatic islets patients with type 2 diabetes (T2D). IAPP secreted conjunction insulin from β regulate glucose metabolism. Here, using a combination analytical biophysical methods vitro, we tested whether EVs isolated healthy T2D modulate formation. We discovered that reduce formation peptide...
Lytic polysaccharide monooxygenase (LPMO) and copper binding protein CopC share a similar mononuclear site. This site is defined by an N-terminal histidine second internal side chain in configuration called the brace. To understand better determinants of reactivity, biochemical structural properties well-described cellulose-specific LPMO from Thermoascus aurantiacus (TaAA9A) compared with that Pseudomonas fluorescens (PfCopC) LPMO-like Bim1 Cryptococcus neoformans. PfCopC not reduced...
Abstract Aggregation of proteins into amyloid deposits is the hallmark several neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. The suggestion that intermediate oligomeric species may be cytotoxic has led to intensified investigations pre-fibrillar oligomers, which are complicated by their transient nature low population. Here we investigate alpha-synuclein enriched a 2-pyridone molecule (FN075) conversion oligomers fibrils. As probed leakage assays, FN075 induced...