A5017281155- Alzheimer's disease research and treatments
- S100 Proteins and Annexins
- Prion Diseases and Protein Misfolding
- RNA Research and Splicing
- Enzyme Structure and Function
- Parkinson's Disease Mechanisms and Treatments
- Genetic Neurodegenerative Diseases
- 14-3-3 protein interactions
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Advanced MRI Techniques and Applications
- Heat shock proteins research
- Trace Elements in Health
- Lipid metabolism and biosynthesis
- Fungal and yeast genetics research
- Immune Response and Inflammation
- Advanced NMR Techniques and Applications
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Photosynthetic Processes and Mechanisms
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Protease and Inhibitor Mechanisms
- Connexins and lens biology
- Thermoregulation and physiological responses
- Advanced Neuroimaging Techniques and Applications
Vilnius University
2017-2025
Czech Academy of Sciences, Institute of Biotechnology
2023-2024
University of Gothenburg
2019-2021
Wallenberg Wood Science Center
2021
Umeå University
2017
S100 calcium-binding protein A9 (S100A9, also known as calgranulin B) is expressed and secreted by myeloid cells under inflammatory conditions, S100A9 can amplify inflammation. There a large increase in expression the brains of patients with neurodegenerative diseases, such Alzheimer's disease, has been suggested to contribute neurodegeneration, but mechanisms are unclear. Here we investigated effects extracellular recombinant on microglia, neurons synapses primary rat brain neuronal-glial...
Quantitative kinetic analysis is critical for understanding amyloid mechanisms. Here we demonstrate the application of generic Finke-Watzky (F-W) two-step nucleation-autocatalytic growth model to concentration-dependent kinetics proinflammatory α-helical S100A9 protein at pH 7.4 and 37 42 °C. The based on two pseudoelementary reaction steps applied without further analytical constraints, its treatment self-assembly demonstrates that initial misfolding β-sheet formation, defined as...
α-Synuclein (aSyn) is an intrinsically disordered protein involved in neurotransmission and synaptic plasticity. The pathological aggregation of this a hallmark synucleinopathies such as Parkinson's disease (PD) or Multiple System Atrophy (MSA). Misfolded aSyn, which primarily originates cell cytosol, transmits between neurons, promoting prion-like propagation. However, the extracellular environments interstitial cerebrospinal fluids (ISF & CSF) play major role its clearance...
Abstract Liquid-liquid phase separation is an emerging field of study, dedicated to understanding the mechanism and role biomolecule assembly into membraneless organelles. One main methods employed in studying protein nucleic acid droplet formation fluorescence microscopy. Despite functioning as excellent tool for monitoring condensation, a few recent reports have presented possible drawbacks using fluorescently labeled particles. It was observed that fluorescent tags could alter process...
Protein liquid-liquid phase separation (LLPS) is a rapidly emerging field of study on biomolecular condensate formation. In recent years, this phenomenon has been implicated in the process amyloid fibril formation, serving as an intermediate step between native protein transition into their aggregated state. The formation fibrils via LLPS demonstrated for number proteins related to neurodegenerative disorders, well other amyloidoses. Despite surge amyloid-related studies, influence end-point...
Alterations in copper ion homeostasis appear coupled to neurodegenerative disorders, but mechanisms are unknown. The cytoplasmic chaperone Atox1 was recently found inhibit amyloid formation vitro of α-synuclein, the amyloidogenic protein Parkinson's disease. As α-synuclein may have copper-dependent functions, and free ions promote formation, it is important characterize interaction with on a molecular level. Here we applied solution-state nuclear magnetic resonance spectroscopy, isotopically...
The calcium-binding protein S100A9 is recognized as an important component of the brain neuroinflammatory response to onset and development neurodegenerative disease. intrinsically amyloidogenic in vivo co-aggregates with amyloid-β peptide α-synuclein Alzheimer's Parkinson's diseases, respectively. It widely accepted that calcium dyshomeostasis plays role these studies have shown elevated levels limit potential for adopt a fibrillar structure. exact mechanism by which exerts its influence on...
The 14-3-3 proteins are a highly conserved adaptor protein family with multi-layer functions, abundantly expressed in the brain. modulate phosphorylation, regulate enzymatic activity and can act as chaperones. Most importantly, they play an important role various neurodegenerative disorders due to their vast interaction partners. Particularly, ζ isoform is known co-localize aggregation tangles both Alzheimer's Parkinson's diseases result of protein–protein interactions. These abnormal clumps...
Calcium-binding S100A8 and S100A9 proteins play a significant role in various disorders due to their pro-inflammatory functions. Substantially, they are also relevant neurodegenerative via the delivery of signals for immune response. However, at same time, can aggregate accelerate progression diseases. Natively, exist as homo- heterodimers, but upon aggregation, form amyloid-like oligomers, fibrils, or amorphous aggregates. In this study, we aimed elucidate aggregation propensities S100A8,...
An interdomain lock modulates the functionality of bacterial periplasmic protease DegP via distinct oligomeric states.
Increasing evidence suggests that the calcium-binding and proinflammatory protein S100A9 is an important player in neuroinflammation-mediated Alzheimer’s disease (AD). The amyloid co-aggregation of with amyloid-β (Aβ) hallmark this pathology. Apolipoprotein E (ApoE) also known to be one genetic risk factors AD. ApoE primarily exists three isoforms, ApoE2 (Cys112/Cys158), ApoE3 (Cys112/Arg158), ApoE4 (Arg112/Arg158). Even though difference lies just two amino acid residues, isoforms produce...
Abstract Protein aggregation in the form of amyloid fibrils has long been associated with onset and development various amyloidoses, including Alzheimer’s, Parkinson’s or prion diseases. Recent studies their fibril formation process have revealed that amyloidogenic protein cross-interactions may impact pathways kinetic parameters, as well structure resulting aggregates. Despite a growing number reports exploring this type interaction, they only cover just small possible pairings. One such...
<title>Abstract</title> The α-synuclein (α-syn) amyloid fibrils are involved in various neurogenerative diseases. Solid-state NMR (ssNMR) has been showed as a powerful tool to study a-syn aggregates. Here, we report the <sup>1</sup>H, <sup>13</sup>C and <sup>15</sup>N back-bone chemical shifts of new α-syn polymorph obtained using proton-detected ssNMR spectroscopy under fast (95 kHz) magic angle spinning conditions. manual shift assignments were cross-validated FLYA algorithm. secondary...
The S100 family consists of calcium binding proteins that are largely known for their contribution to the neuroinflammatory processes. They associated with various cardiac and neurological functions as well related diseases. A few can form unspecific or amyloid aggregates in neuropathologies thus play a part dementia pathogenesis. Among all proteins, S100B S100A9 aggregation properties most investigated, however, there is lack studies regarding other members. In particular, S100A1 S100A8...
Neuronal cell death induced by membrane damage is one of the major hallmarks neurodegenerative diseases. Neuroinflammation precedes loss neurons; however, whether and how inflammation-related proteins contribute to integrity remains unknown. We employed a range biophysical tools, including high-speed atomic force microscopy, fluorescence spectroscopy, electrochemical impedance ascertain pro-inflammatory protein S100A8 induces alterations in biomimetic lipid membranes upon interaction. Our...
Liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a rapidly emerging field study, aimed at understanding the process biomolecular condensate formation its role in cellular functions. LLPS has been shown to be responsible for generation promyelocytic leukemia protein bodies, stress granules, intrinsically disordered condensates. Recently, it discovered that different neurodegenerative disease-related proteins, such as alpha-synuclein (related Parkinson's disease)...
Abstract The 14-3-3 is a highly conserved adaptor protein family with multi-layer functions, abundantly expressed in the brain. proteins modulate phosphorylation, regulate enzymatic activity and can act as chaperones. Most importantly, they play an important role various neurodegenerative disorders due to their vast interaction partners. Particularly, 14-3-3ξ isoform known co-localize aggregation tangles both Alzheimer’s Parkinson’s diseases result of protein-protein interactions. These...
Protein quality control is an essential cellular function mainly executed by a vast array of different proteases and molecular chaperones. One the bacterial HtrA (high temperature requirement A) protein family members, homo-oligomeric DegP-protease, plays crucial role in Escherichia coli ( E. ) machinery removing unfolded proteins or preventing their aggregation chaperoning them to final folded state within periplasm. DegP contains two regulatory PDZ domains, which play key roles substrate...