Journal: Cellular and Molecular Life Sciences

Abbreviation

Cell. Mol. Life Sci.

Publisher

Springer

Journal Volumes

ISSN

1420-682X
1420-9071

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Publications1 - 10 of 28
  • FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases
    Item type: Journal Article
    Stefanova, Debora; Olszewski, Dominik; Glitscher, Mirco; et al. (2024)
    Cellular and Molecular Life Sciences
    The development of antiviral strategies is a key task of biomedical research, but broad-spectrum virus inhibitors are scarce. Here we show that fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors reduce infection of several cell types with DNA and RNA viruses by blocking early stages of infection, but not viral cell association. Unexpectedly, their antiviral activity was largely independent of FGFR kinase inhibition. RNA profiling showed upregulation of interferon response genes by FGFR inhibitors, but their expression did not correlate with the antiviral activity in infected cells. Using bioinformatics analysis of kinome data, targeted kinase assays, siRNA-mediated knock-down and pharmacological inhibition experiments, we show that blockade of Src family kinases, in particular Lyn, is mainly responsible for the antiviral activity of FGFR inhibitors. These results identify FGFR inhibitors as broad-spectrum antiviral agents and suggest the poorly studied Lyn kinase as a promising target for the treatment of viral infections.
  • Functions of the RIP kinase family members in the skin
    Item type: Review Article
    Urwyler‑Rösselet, Corinne; Tanghe, Giel; Devos, Michael; et al. (2023)
    Cellular and Molecular Life Sciences
    The receptor interacting protein kinases (RIPK) are a family of serine/threonine kinases that are involved in the integration of various stress signals. In response to several extracellular and/or intracellular stimuli, RIP kinases engage signaling cascades leading to the activation of NF-κB and mitogen-activated protein kinases, cell death, inflammation, differentiation and Wnt signaling and can have kinase-dependent and kinase-independent functions. Although it was previously suggested that seven RIPKs are part of the RIPK family, phylogenetic analysis indicates that there are only five genuine RIPKs. RIPK1 and RIPK3 are mainly involved in controlling and executing necroptosis in keratinocytes, while RIPK4 controls proliferation and differentiation of keratinocytes and thereby can act as a tumor suppressor in skin. Therefore, in this review we summarize and discuss the functions of RIPKs in skin homeostasis as well as the signaling pathways involved.
  • Protein phosphatases and their potential implications in neuroprotective processes
    Item type: Journal Article
    Gee, C.E.; Mansuy, Isabelle (2005)
    Cellular and Molecular Life Sciences
  • Biosynthesis of isoprenoids via the non mevalonate pathway
    Item type: Review Article
    Eisenreich, W.; Bacher, Adelbert; Arigoni, D.; et al. (2004)
    Cellular and Molecular Life Sciences
  • RNA recognition by double-stranded RNA binding domains
    Item type: Review Article
    Masliah, Grégoire; Barraud, Pierre; Allain, Frédéric H.-T. (2013)
    Cellular and Molecular Life Sciences
  • Eph- and ephrin-dependent mechanisms in tumor and stem cell dynamics
    Item type: Journal Article
    Gucciardo, Erika; Sugiyama, Nami; Lehti, Kaisa (2014)
    Cellular and Molecular Life Sciences
  • Neurobiological research on N,N-dimethyltryptamine (DMT) and its potentiation by monoamine oxidase (MAO) inhibition: from ayahuasca to synthetic combinations of DMT and MAO inhibitors
    Item type: Review Article
    Egger, Klemens; Aicher, Helena D.; Cumming, Paul; et al. (2024)
    Cellular and Molecular Life Sciences
    The potent hallucinogen N,N-dimethyltryptamine (DMT) has garnered significant interest in recent years due to its profound effects on consciousness and its therapeutic psychopotential. DMT is an integral (but not exclusive) psychoactive alkaloid in the Amazonian plant-based brew ayahuasca, in which admixture of several β-carboline monoamine oxidase A (MAO-A) inhibitors potentiate the activity of oral DMT, while possibly contributing in other respects to the complex psychopharmacology of ayahuasca. Irrespective of the route of administration, DMT alters perception, mood, and cognition, presumably through agonism at serotonin (5-HT) 1A/2A/2C receptors in brain, with additional actions at other receptor types possibly contributing to its overall psychoactive effects. Due to rapid first pass metabolism, DMT is nearly inactive orally, but co-administration with β-carbolines or synthetic MAO-A inhibitors (MAOIs) greatly increase its bioavailability and duration of action. The synergistic effects of DMT and MAOIs in ayahuasca or synthetic formulations may promote neuroplasticity, which presumably underlies their promising therapeutic efficacy in clinical trials for neuropsychiatric disorders, including depression, addiction, and post-traumatic stress disorder. Advances in neuroimaging techniques are elucidating the neural correlates of DMT-induced altered states of consciousness, revealing alterations in brain activity, functional connectivity, and network dynamics. In this comprehensive narrative review, we present a synthesis of current knowledge on the pharmacology and neuroscience of DMT, β-carbolines, and ayahuasca, which should inform future research aiming to harness their full therapeutic potential.
  • Wnt signaling
    Item type: Review Article
    Ille, F.; Sommer, L. (2005)
    Cellular and Molecular Life Sciences
  • Formation of starch in plant cells
    Item type: Review Article
    Pfister, Barbara; Zeeman, Samuel C. (2016)
    Cellular and Molecular Life Sciences
    Starch-rich crops form the basis of our nutrition, but plants have still to yield all their secrets as to how they make this vital substance. Great progress has been made by studying both crop and model systems, and we approach the point of knowing the enzymatic machinery responsible for creating the massive, insoluble starch granules found in plant tissues. Here, we summarize our current understanding of these biosynthetic enzymes, highlighting recent progress in elucidating their specific functions. Yet, in many ways we have only scratched the surface: much uncertainty remains about how these components function together and are controlled. We flag-up recent observations suggesting a significant degree of flexibility during the synthesis of starch and that previously unsuspected non-enzymatic proteins may have a role. We conclude that starch research is not yet a mature subject and that novel experimental and theoretical approaches will be important to advance the field.
  • Glycine receptors and glycine transporters: targets for novel analgesics?
    Item type: Review Article
    Zeilhofer, Hanns U.; Acuña, Mario A.; Gingras, Jacinthe; et al. (2018)
    Cellular and Molecular Life Sciences
    Glycinergic neurotransmission has long been known for its role in spinal motor control. During the last two decades, additional functions have become increasingly recognized—among them is a critical contribution to spinal pain processing. Studies in rodent pain models provide proof-of-concept evidence that enhancing inhibitory glycinergic neurotransmission reduces chronic pain symptoms. Apparent strategies for pharmacological intervention include positive allosteric modulators of glycine receptors and modulators or inhibitors of the glial and neuronal glycine transporters GlyT1 and GlyT2. These prospects have led to drug discovery efforts in academia and in industry aiming at compounds that target glycinergic neurotransmission with high specificity. Available data show promising analgesic efficacy. Less is currently known about potential unwanted effects but the presence of glycinergic innervation in CNS areas outside the nociceptive system prompts for a careful evaluation not only of motor function, but also of potential respiratory impairment and addictive properties.
Publications1 - 10 of 28