Jonathan Teuffel

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About Jonathan Teuffel:

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SEEK ID: https://publications.h-its.org/people/159

Location: Germany

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Joined: 2nd Nov 2022

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Molecular and Cellular Modeling

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Heidelberg Institute for Theoretical Studies

Country: Germany

City: Heidelberg

Web page: https://www.h-its.org

Showing 5 out of a possible 37 Publications Advanced Publications list for this Person with search and filtering

Structural bioinformatics approach to exploring transient binding pockets in proteins

Molecular and Cellular Modeling

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Date Published: 18th Dec 2024

Publication Type: Bachelor's Thesis

Citation: Faculty of Biosciences and Faculty of Chemistry and Earth Sciences, Ruprecht-Karls University, Heidelberg

Created: 18th Dec 2024 at 13:50

Impact of an irreversible β-galactosylceramidase inhibitor on the lipid profile of zebrafish embryos

Molecular and Cellular Modeling

Abstract

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Authors: Jessica Guerra, Mirella Belleri, Giulia Paiardi, Chiara Tobia, Davide Capoferri, Marzia Corli, Elisa Scalvini, Marco Ghirimoldi, Marcello Manfredi, Rebecca C. Wade, Marco Presta, Luca Mignani

Date Published: 1st Dec 2024

Publication Type: Journal

DOI: 10.1016/j.csbj.2024.03.023

Citation: Computational and Structural Biotechnology Journal 23:1397-1407

Created: 7th May 2024 at 17:29, Last updated: 19th Dec 2024 at 13:22

Computational screening of the effects of mutations on protein-protein off-rates and dissociation mechanisms by τRAMD

Molecular and Cellular Modeling

Abstract (Expand)

Abstract The dissociation rate, or its reciprocal, the residence time (τ), is a crucial parameter for understanding the duration and biological impact of biomolecular interactions. Accurate prediction …

Authors: Giulia D’Arrigo, Daria B. Kokh, Ariane Nunes-Alves, Rebecca C. Wade

Date Published: 1st Dec 2024

Publication Type: Journal

DOI: 10.1038/s42003-024-06880-5

Citation: Commun Biol 7(1),1159

Created: 23rd Oct 2024 at 19:40, Last updated: 23rd Oct 2024 at 19:41

Comprehensive characterization of the neurogenic and neuroprotective action of a novel TrkB agonist using mouse and human stem cell models of Alzheimer’s disease

Molecular and Cellular Modeling

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Abstract Background Neural stem cell (NSC) proliferation and differentiation in the mammalian brain decreases to minimal levels postnatally. Nevertheless, neurogenic niches persist in the adult cortex …rtheless, neurogenic niches persist in the adult cortex and hippocampus in rodents, primates and humans, with adult NSC differentiation sharing key regulatory mechanisms with development. Adult neurogenesis impairments have been linked to Alzheimer’s disease (AD) pathology. Addressing these impairments by using neurotrophic factors is a promising new avenue for therapeutic intervention based on neurogenesis. However, this possibility has been hindered by technical difficulties of using in-vivo models to conduct screens, including working with scarce NSCs in the adult brain and differences between human and mouse models or ethical limitations. Methods Here, we use a combination of mouse and human stem cell models for comprehensive in-vitro characterization of a novel neurogenic compound, focusing on the brain-derived neurotrophic factor (BDNF) pathway. The ability of ENT-A011, a steroidal dehydroepiandrosterone derivative, to activate the tyrosine receptor kinase B (TrkB) receptor was tested through western blotting in NIH-3T3 cells and its neurogenic and neuroprotective action were assessed through proliferation, cell death and Amyloid-β (Aβ) toxicity assays in mouse primary adult hippocampal NSCs, mouse embryonic cortical NSCs and neural progenitor cells (NPCs) differentiated from three human induced pluripotent stem cell lines from healthy and AD donors. RNA-seq profiling was used to assess if the compound acts through the same gene network as BDNF in human NPCs. Results ENT-A011 was able to increase proliferation of mouse primary adult hippocampal NSCs and embryonic cortical NSCs, in the absence of EGF/FGF, while reducing Aβ-induced cell death, acting selectively through TrkB activation. The compound was able to increase astrocytic gene markers involved in NSC maintenance, protect hippocampal neurons from Αβ toxicity and prevent synapse loss after Aβ treatment. ENT-A011 successfully induces proliferation and prevents cell death after Aβ toxicity in human NPCs, acting through a core gene network shared with BDNF as shown through RNA-seq. Conclusions Our work characterizes a novel BDNF mimetic with preferable pharmacological properties and neurogenic and neuroprotective actions in Alzheimer’s disease via stem cell-based screening, demonstrating the promise of stem cell systems for short-listing competitive candidates for further testing.

Authors: Despoina Charou, Thanasis Rogdakis, Alessia Latorrata, Maria Valcarcel, Vasileios Papadogiannis, Christina Athanasiou, Alexandros Tsengenes, Maria Anna Papadopoulou, Dimitrios Lypitkas, Matthieu D. Lavigne, Theodora Katsila, Rebecca C. Wade, M. Zameel Cader, Theodora Calogeropoulou, Achille Gravanis, Ioannis Charalampopoulos

Date Published: 1st Dec 2024

Publication Type: Journal

DOI: 10.1186/s13287-024-03818-w

Citation: Stem Cell Res Ther 15(1),200

Created: 5th Nov 2024 at 22:34, Last updated: 5th Nov 2024 at 22:34

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models

Molecular and Cellular Modeling

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BACKGROUND: The EF-hand Ca 2+ sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of …ancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca 2+ ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75–94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts. METHODS: We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models. RESULTS: We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca 2+ cycling and prevents β-adrenergic receptor–triggered Ca 2+ imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca 2+ pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo. CONCLUSIONS: S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.

Authors: Dorothea Kehr, Julia Ritterhoff, Manuel Glaser, Lukas Jarosch, Rafael E. Salazar, Kristin Spaich, Karl Varadi, Jennifer Birkenstock, Michael Egger, Erhe Gao, Walter J. Koch, Max Sauter, Marc Freichel, Hugo A. Katus, Norbert Frey, Andreas Jungmann, Cornelius Busch, Paul J. Mather, Arjang Ruhparwar, Martin Busch, Mirko Völkers, Rebecca C. Wade, Patrick Most

Date Published: 21st Nov 2024

Publication Type: Journal

DOI: 10.1161/CIRCULATIONAHA.123.066961

Citation: Circulation,CIRCULATIONAHA.123.066961

Created: 13th Feb 2025 at 11:48, Last updated: 13th Feb 2025 at 11:48

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