Article
Pharmacology & Pharmacy
Sebastian Peters, Eva Wirkert, Sabrina Kuespert, Rosmarie Heydn, Siw Johannesen, Anita Friedrich, Susanne Mailaender, Sven Korte, Lars Mecklenburg, Ludwig Aigner, Tim-Henrik Bruun, Ulrich Bogdahn
Summary: Through the study of the pharmacology, safety, and tolerability of LNA Gapmer Antisense Oligonucleotide NVP-13 in nonhuman primates, we found that it effectively reduces the expression of TGFBR2, decreases TGF beta signal transduction, and enhances neurogenic niche activity. The use of NVP-13 in cynomolgus monkeys did not result in any adverse events.
Article
Cell Biology
Xinyuan Liu, Jian Xu, Bingbing Shen, Jichuan Xu, Jianxin Jiang
Summary: Pancreatic cancer (PC) is the fourth leading cause of cancer-related death worldwide, with a survival rate below 5%. Abnormal proliferation and distant metastasis are major challenges for the diagnosis and treatment of PC, making it crucial for researchers to understand the molecular mechanisms underlying PC proliferation and metastasis. This study found that USP33, a member of the deubiquitinating enzyme family, is upregulated in PC samples and cells, and its high expression is associated with poor prognosis. Functional experiments showed that USP33 overexpression promotes PC cell proliferation, migration, and invasion, while inhibition of USP33 has the opposite effect. The study also identified TGFBR2 as a potential binding protein of USP33 and revealed a positive feedback loop between USP33 and the TGF-beta signaling pathway.
CELL DEATH & DISEASE
(2023)
Review
Immunology
Rachel V. Jimenez, Alexander J. Szalai
Summary: CRP levels are typically low in healthy individuals, but can rise rapidly in response to tissue damage and inflammation. It is commonly believed that CRP's biological actions are only evident when blood levels are elevated, however studies have shown that even at baseline levels CRP exerts important biological effects.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Developmental Biology
Shunji Jia, Anming Meng
Summary: The TGF beta signaling family is evolutionarily conserved in metazoans and plays diverse roles in embryonic development, adult tissue homeostasis, and human diseases by regulating cell proliferation, differentiation, adhesion, migration, and apoptosis. The molecular mechanisms and key functions of TGF beta subfamily pathways in mesendoderm induction, dorsoventral patterning, laterality development, and tissue/organ formation have been extensively investigated.
Article
Biochemistry & Molecular Biology
Amannisa Tuersuntuoheti, Qinshan Li, Yu Teng, Xiaolu Li, Rong Huang, Yan Lu, Kai Li, Junbo Liang, Shiying Miao, Wei Wu, Wei Song
Summary: This study demonstrates the role of YWK-II/APLP2 in negatively regulating the duration and intensity of TGF-beta/Smad signaling. By promoting the degradation of the TGFBR2 protein, YWK-II/APLP2 inhibits TGF-beta signaling. Aberrantly high expression of YWK-II/APLP2 may counteract the growth inhibition mediated by TGF-beta signaling and contribute to carcinogenesis in malignancies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Franciscus C. Vermeer, Jeroen Bremer, Robert J. Sietsma, Aileen Sandilands, Robyn P. Hickerson, Marieke C. Bolling, Anna M. G. Pasmooij, Henny H. Lemmink, Morris A. Swertz, Nine V. A. M. Knoers, K. Joeri van der Velde, Peter C. van den Akker
Summary: Epidermolysis bullosa is a genetic skin condition characterized by skin fragility caused by gene variants, with treatment currently focused on symptom relief. Exon skipping shows potential as a therapeutic strategy for EB, with the severity of the disease linked to gene involvement and variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Carme Fabrega, Anna Avino, Natalia Navarro, Andreia F. Jorge, Santiago Grijalvo, Ramon Eritja
Summary: In this study, the conjugation of oligonucleotides with lipids and peptides for the development of therapeutics with improved pharmacokinetics is reviewed.
Review
Pharmacology & Pharmacy
Marta Pascual-Gilabert, Arturo Lopez-Castel, Ruben Artero
Summary: This article provides a comprehensive overview of recent drug development programs for DM1, including new chemical entities, drug repurposing, oligonucleotide, and gene therapy approaches. Among these, repurposing tideglusib, mexiletine, or metformin may have the most potential to receive marketing authorization for DM1.
DRUG DISCOVERY TODAY
(2021)
Article
Cell Biology
Monica Stanwick, Courtney Barkley, Rosa Serra, Andrew Kruggel, Amy Webb, Yue Zhao, Maciej Pietrzak, Chandler Ashman, Allie Staats, Shifa Shahid, Sarah B. Peters
Summary: Transforming growth factor beta (TGF beta) plays an important role in tooth morphogenesis and mineralization. Deletion of Tgfbr2 in dental pulp mesenchyme leads to significant defects in bone and teeth, including reduced mineralization and short roots. Tgfbr2 deletion disrupts axon-like structures and reduces innervation in teeth. Downregulation of mineralization-related and neuronal genes is observed in Tgfbr2-deleted dental pulp. Tgfbr2 in the dental pulp mesenchyme regulates differentiation and the ability to guide neurite outgrowth during tooth mineralization and innervation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Maria Gagliardi, Ana Tari Ashizawa
Summary: ASOs are a novel and promising class of drugs used to selectively inhibit the translation of disease-associated genes. Challenges in ASO delivery and stability require strategic approaches to overcome these limitations for their full potential in precision medicine.
Review
Oncology
Prithi Raguraman, Akilandeswari Ashwini Balachandran, Suxiang Chen, Sarah D. Diermeier, Rakesh N. Veedu
Summary: Splicing plays a crucial role in protein diversity, but aberrant splicing can contribute to cancer development. Antisense oligonucleotides (AOs) have the potential to modulate splicing mechanisms and show promise as a targeted therapy for cancer treatment. Delivery strategies for efficient AO uptake into cells are being continuously developed to enhance their therapeutic efficacy.
Review
Medicine, General & Internal
Piotr K. Zakrzewski
Summary: Endometrial cancer is a major gynecological cancer among women in their menopausal and postmenopausal age, and the canonical TGF beta pathway plays a crucial role in its development and progression. The TGF beta cascade can act as both a tumor suppressor and tumor promoter, with its effects on endometrial cancer cells depending on the cancer disease stage.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Chisato Terada, Seiya Kawamoto, Asako Yamayoshi, Tsuyoshi Yamamoto
Summary: Oligonucleotide therapeutics have made significant progress in the treatment of diseases, but are still limited by side effects. This review aims to explore avenues for symbiotic engineering of oligonucleotide therapeutics through the discussion of physicochemical characteristics, in order to achieve more effective and safer drugs.
Review
Pharmacology & Pharmacy
Lars Weidolf, Anders Bjorkbom, Anders Dahlen, Marie Elebring, Peter Gennemark, Mikko Holtta, David Janzen, XueQing Li, Shalini Andersson
Summary: This review article highlights the significant differences in drug properties between antisense oligonucleotides (ASOs) and traditional small-molecule therapeutics, focusing on the distribution and biotransformation characteristics of nonconjugated and conjugated ASOs. Understanding the disposition of ASOs is crucial for both nonclinical and clinical predictions, as well as for communication with health agencies to optimize ASO therapy for patients.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Michael Latour, Nam-Gu Her, Santosh Kesari, Elmar Nurmemmedov
Summary: The WNT signaling pathway plays a crucial role in glioblastoma genesis and therapy resistance, presenting a therapeutic challenge. Current targeted therapies under clinical investigation may offer new treatment options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Paolo Gelosa, Elisabetta Bonfanti, Laura Castiglioni, Jose Maria Delgado-Garcia, Agnes Gruart, Lucia Fontana, Marco Gotti, Elena Tremoli, Davide Lecca, Marta Fumagalli, Mauro Cimino, Ludwig Aigner, Maria P. Abbracchio, Luigi Sironi
PHARMACOLOGICAL RESEARCH
(2019)
Article
Medicine, Research & Experimental
Mahesh Kandasamy, Ajisha Yesudhas, G. P. Poornimai Abirami, Risna Kanjirassery Radhakrishnan, Syed Aasish Roshan, Esther Johnson, Vijaya Roobini Ravichandran, Abir Biswas, Sellathamby Shanmugaapriya, Muthuswamy Anusuyadevi, Ludwig Aigner
MEDICAL HYPOTHESES
(2019)
Article
Food Science & Technology
Dorrain Yanwen Low, Sophie Lefevre-Arbogast, Raul Gonzalez-Dominguez, Mireia Urpi-Sarda, Pierre Micheau, Melanie Petera, Delphine Centeno, Stephanie Durand, Estelle Pujos-Guillot, Aniko Korosi, Paul J. Lucassen, Ludwig Aigner, Cecile Proust-Lima, Boris P. Hejblum, Catherine Helmer, Cristina Andres-Lacueva, Sandrine Thuret, Cecilia Samieri, Claudine Manach
MOLECULAR NUTRITION & FOOD RESEARCH
(2019)
Article
Neurosciences
Lara Bieler, Michael Vogl, Michael Kirchinger, Corinna Urmann, Herbert Riepl, Christine Bandtlow, Lars Klimaschewski, Ludwig Aigner, Sebastien Couillard-Despres
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Clinical Neurology
Pasquale Romanelli, Lara Bieler, Cornelia Scharler, Karin Pachler, Christina Kreutzer, Pia Zaunmair, Dominika Jakubecova, Heike Mrowetz, Bruno Benedetti, Francisco J. Rivera, Ludwig Aigner, Eva Rohde, Mario Gimona, Dirk Strunk, Sebastien Couillard-Despres
FRONTIERS IN NEUROLOGY
(2019)
Article
Multidisciplinary Sciences
David Gate, Naresha Saligrama, Olivia Leventhal, Andrew C. Yang, Michael S. Unger, Jinte Middeldorp, Kelly Chen, Benoit Lehallier, Divya Channappa, Mark B. De Los Santos, Alisha McBride, John Pluvinage, Fanny Elahi, Grace Kyin-Ye Tam, Yongha Kim, Michael Greicius, Anthony D. Wagner, Ludwig Aigner, Douglas R. Galasko, Mark M. Davis, Tony Wyss-Coray
Article
Neurosciences
Julia Marschallinger, Tal Iram, Macy Zardeneta, Song E. Lee, Benoit Lehallier, Michael S. Haney, John V. Pluvinage, Vidhu Mathur, Oliver Hahn, David W. Morgens, Justin Kim, Julia Tevini, Thomas K. Felder, Heimo Wolinski, Carolyn R. Bertozzi, Michael C. Bassik, Ludwig Aigner, Tony Wyss-Coray
NATURE NEUROSCIENCE
(2020)
Correction
Neurosciences
Julia Marschallinger, Tal Iram, Macy Zardeneta, Song E. Lee, Benoit Lehallier, Michael S. Haney, John V. Pluvinage, Vidhu Mathur, Oliver Hahn, David W. Morgens, Justin Kim, Julia Tevini, Thomas K. Felder, Heimo Wolinski, Carolyn R. Bertozzi, Michael C. Bassik, Ludwig Aigner, Tony Wyss-Coray
NATURE NEUROSCIENCE
(2020)
Article
Clinical Neurology
Julia Marschallinger, Barbara Altendorfer, Edward Rockenstein, Miriam Holztrattner, Julia Garnweidner-Raith, Nadine Pillichshammer, Iris Leister, Birgit Hutter-Paier, Katharina Strempfl, Michael S. Unger, Mansoor Chishty, Thomas Felder, Mary Johnson, Johannes Attems, Eliezer Masliah, Ludwig Aigner
Article
Urology & Nephrology
Elena E. Keller, Irina Patras, Ioan Hutu, Karin Roider, Karl-Dietrich Sievert, Ludwig Aigner, Guenter Janetschek, Lukas Lusuardi, Reinhold Zimmermann, Sophina Bauer
NEUROUROLOGY AND URODYNAMICS
(2020)
Article
Neurosciences
Kathrin M. Kniewallner, Diana M. Bessa de Sousa, Michael S. Unger, Heike Mrowetz, Ludwig Aigner
FRONTIERS IN NEUROSCIENCE
(2020)
Article
Pharmacology & Pharmacy
Sebastian Peters, Eva Wirkert, Sabrina Kuespert, Rosmarie Heydn, Siw Johannesen, Anita Friedrich, Susanne Mailaender, Sven Korte, Lars Mecklenburg, Ludwig Aigner, Tim-Henrik Bruun, Ulrich Bogdahn
Summary: Through the study of the pharmacology, safety, and tolerability of LNA Gapmer Antisense Oligonucleotide NVP-13 in nonhuman primates, we found that it effectively reduces the expression of TGFBR2, decreases TGF beta signal transduction, and enhances neurogenic niche activity. The use of NVP-13 in cynomolgus monkeys did not result in any adverse events.
Article
Pharmacology & Pharmacy
Judith Kozole, Rosmarie Heydn, Eva Wirkert, Sabrina Kuespert, Ludwig Aigner, Tim-Henrik Bruun, Ulrich Bogdahn, Sebastian Peters, Siw Johannesen
Summary: This pilot study analyzed the molecular effects of a single high-dose G-CSF application on different regions of the rodent brain. The results showed minor suppressive or stimulatory effects on neurogenic and non-neurogenic differentiation markers, with an upregulation observed in the cerebellum and hypothalamus.
Review
Clinical Neurology
Iris Leister, Thomas Haider, Georg Mattiassich, John L. K. Kramer, Lukas D. Linde, Adnan Pajalic, Lukas Grassner, Barbara Altendorfer, Herbert Resch, Stephanie Aschauer-Wallner, Ludwig Aigner
NEUROREHABILITATION AND NEURAL REPAIR
(2020)