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| CHINMULTIHIT – Identifikácia malých molekúl z tradičných čínskych bylín na multicieľovú terapiu neurodegenerat ívnych ochorení a objasnenie mechanizmu účinku | |
| Discovery and Mechanism of Small Molecules from Traditional Chinese Herbs for Multitarget directed Therapy of Neurodegenerative Diseases | |
| Program: | Bilateral – other |
| Project leader: | doc. RNDr. Gažová Zuzana, DrSc. |
| Annotation: | Protein misfolding neurodegenerative diseases (NDDs), such as Alzheimer\’s and Parkinson\’s diseases, result inextensive cellular and neuronal loss within the central nervous system. Despite the distinct manifestations of thesedisorders, they share several common pathogenic mechanisms. Current pharmacological interventions areineffective. Moreover, the complexity of NDDs necessitates innovative therapeutic approaches. In this project, thenovel "multi-target-directed ligands" (MTDLs) strategy will be employed as it focuses on development of novelcompounds modulating multiple factors simultaneously. We will focus on Chinese herbs – Angelica sinensis,Ligusticum chuanxiong, and Cinnamomum cassia. The project aims to explore the anti-aggregation potential ofthese herbal extracts and their derivatives targeting both Aβ peptide and α -synuclein, showcasing neuroprotectiveand anti-inflammatory properties to pave the way for the development of novel t herapeutic strategies for NDDs.The project combines the expertise and experience of both research teams in the field of protein misfolding andNDDs pathology, allowing us to acquire complex data with the aid of complementary approaches, leading to thesuggestion of possible alternatives of therapy against these devastating diseases. Moreover, this collaborativeresearch partnership will present an excellent opportunity for both teams\’ young members to learn new techniquesin the well-equipped laboratories at East China University and IEP SAS and gain new experience by working in aninternational scientific environment. |
| Duration: | 1.7.2024 – 30.6.2026 |
| LEAPAB – Inhibícia agregácie A-beta peptidov proteínmi vyskytujúcimi sa počas neskorej embryogenézy: nový prístup liečby Alzheimerovej choroby | |
| Inhibition of A-beta Peptides Aggregation by Late Embryogenesis Abundant Proteins: A New Approach for Alzheimer’s Disease Treatment | |
| Program: | Bilateral – other |
| Project leader: | RNDr. Bednáriková Zuzana, PhD. |
| Annotation: | Alzheimer’s disease (AD) is the most common neurodegenerative disorder, sharing unclear pathophysiology and massive social costs. Today, more than 55 million people have been diagnosed with AD, which is forecast to increase more than twice by 2050. AD is tightly associated with the formation of deposits containing amyloid β (Aβ) peptide organized into insoluble amyloid fibrils. Despite numerous contemporary studies focused on reducing Aβ aggregation, a cure for AD has not yet been found. Our project intends to implement the elements of molecular mechanisms underlying the remarkable phenomenon of plant desiccation tolerance and develop a new Aβ anti-aggregation strategy. Late Embryogenesis Abundant proteins (LEAPs) are markedly induced upon desiccation and can stabilize the native structure of proteins and membranes by a mechanism that is not fully understood. The primary project aim is to investigate the structural properties of Ramonda serbica LEAPs and their interactions with Aβ peptides and aggregation. Firstly, we will recombinantly produce LEAPs with the highest potential to inhibit Aβ aggregation. Further, we will analyze LEAPs’ secondary structure under different conditions, focusing on their order-to-disorder transitions. The final aim is to identify Aβ/LEAPs interactions and assess the Aβ anti-aggregation potential of LEAPs in vitro, which will impact the development of new strategies for AD treatment. The collaborating teams involved in this project (Slovak – IEP SAS and Serbian – IMGGE) were selected based on their expertise in protein production, protein structure analysis and amyloid aggregation. The expertise transfer between partner laboratories will be ensured by mutual training of PhD and postdoc researchers involved in the project. |
| Duration: | 1.4.2024 – 31.12.2025 |
| Azobenzénové deriváty ako potenciálne terapeutiká pre Alzheimerovu chorobu | |
| Azobenzenes as potential Alzheimer\’s theranostic agents | |
| Program: | Mobility |
| Project leader: | RNDr. Bednáriková Zuzana, PhD. |
| Annotation: | Amyloid fibrils of amyloid β (Aβ) peptides are a neuropathological feature of Alzheimer\’s disease (AD). AD is one of the world\’s fastest-growing neurological diseases with substantial economic and societal impact, but no cure is currently available. Therefore, the exploration of novel treatment approaches is in high demand. The project\’s main objective is to study the ability of azobenzene molecules to affect targets associated with the amyloid cascade of AD pathogenesis. The project will employ the lever-like potential of azobenzene molecules to dissociate fibrillar aggregates of Aβ peptides and inhibit the proteolytic activity of β-secretase. We will integrate in vitro, in silico, and cells workflow to find a possible alternative therapy against this devastating disease. Moreover, this collaborative research partnership will present an excellent opportunity for both teams\’ young members to learn new techniques in the well-equipped laboratories at the Polish and Slovak Academies of Sciences and gain new experience by working in an international scientific environment. |
| Duration: | 1.1.2023 – 31.12.2024 |
| ANOMATY – Interakcie amyloidných fibríl a nanočastíc pre biomedicínske, biochemické a inžinierske aplikácie | |
| Interactions of nanoparticles with amyloid fibrils: from therapy to nanomaterials | |
| Program: | Bilateral – other |
| Project leader: | doc. RNDr. Gažová Zuzana, DrSc. |
| Annotation: | Nanoparticles represent a powerful platform with a large potential for biomedicine and engineering applications.The formation of amyloid aggregates is unfavorable in vivo as they are associated with the pathogenesis of many human diseases, yet, amyloid fibrils have the potential to be engineered into novel materials. However, there is still little known about the interactions between amyloid fibrils and nanoparticles that can provide new enhanced NPs functions. The project aims to investigate the interaction of amyloid fibrils formed from native globular proteins and nanoparticles to utilize or enhance the NPs applications as catalysts in engineering applications or possible disaggregation agents to treat amyloid-related diseases (Alzheimer´s disease, diabetes mellitus). We will determine the relationship between amyloid fibrils (formed from lysozyme, insulin, and α -lactalbumin) and Au-, Ag- and Pd –nanoparticles with different surface chemistry (size, charge, functionalization). Moreover, we will perform a systematic study of globular proteins\’ propensity to form amyloid fibrils with controlled properties. The proposed objectives will be achieved by combining experimental techniques with computational methods routinely used in respective scientific teams. Moreover, the data about fibrils\’ structural and physico-chemical properties might fill the empty spaces in a big biology puzzle – pathophysiology of amyloid-related diseases. |
| Duration: | 1.1.2022 – 31.12.2023 |
| Stabilita a agregácia globulárnych proteínov v prítomnosti biokompatibilných iónových kvapalín | |
| Stability and aggregation of globular proteins in the presence of biocompatible ionic liquids | |
| Program: | Mobility |
| Project leader: | RNDr. Fedunová Diana, PhD. |
| Duration: | 1.1.2021 – 31.12.2022 |
National
| Objasnenie počiatočných štádií amyloidnej agregácie proteínov – od mechanizmu k terapii | |
| Unraveling the early events of protein amyloid aggregation – from mechanism to therapy | |
| Program: | VEGA |
| Project leader: | doc. RNDr. Gažová Zuzana, DrSc. |
| Annotation: | Structural changes of poly/peptides leading to the formation of amyloid aggregates are associated with incurablediseases, like Alzheimer\’s disease or diabetes. While the general mechanisms of fibril formation and theircharacterization are well reported, the early events during poly/peptide fibrillation are still unclear. The project isfocused on understanding the early events mechanisms leading to the formation of pre-fibrillar (partially un/foldedintermediates, nuclei, oligomers) and fibrillar amyloid aggregates of selected globular and intrinsically disorderedproteins. Our focus will be the study of the kinetics of pre-fibrillar structures formation, their morphology, andcytotoxicity, under various experimental conditions, and in the presence of selected interacting partners (smallmolecules, nanoparticles). The obtained results will contribute to understanding the early events of amyloidaggregation and identifying the inhibitors with therapeutic potential for amyloid diseases. |
| Duration: | 1.1.2021 – 31.12.2024 |
| MULTIHIT – Multifunkčné inhibítory poly/peptidov spojených s Alzheimerovou chorobou | |
| Multi-target inhibitors of poly/peptides associated with Alzheimer´s disease | |
| Program: | SRDA |
| Project leader: | doc. RNDr. Gažová Zuzana, DrSc. |
| Duration: | 1.7.2019 – 1.6.2023 |
| Štúdium pôsobenia hybridných molekúl na amyloidnú agregáciu globulárnych a prirodzene rozbalených proteínov | |
| – | |
| Program: | DoktoGrant |
| Project leader: | RNDr. Borovská Barbora |
| Duration: | 1.1.2022 – 31.12.2022 |