Signaling networks in MS: A systems-based approach to developing new pharmacological therapies
| Autor: | Leonidas G. Alexopoulos, Tomas Olsson, Roland Martin, Elena Schwartz, Ekaterina Kotelnikova, Ioannis N. Melas, Julio Saez-Rodriguez, P. Villoslada, Friedemann Paul, Albert Zamora, Jose Manuel Mas, Laura Artigas, Jesper Tegnér, Gilad Silberberg, Dimitris E Messinis, Ilya Mazo, Narsis A. Kiani, Mar Masso, Marti Bernardo-Faura |
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| Přispěvatelé: | University of Zurich, Villoslada, Pablo |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Multiple Sclerosis
medicine.medical_treatment Systems biology 610 Medicine & health Disease Biology Bioinformatics stat Immune system Drug Discovery medicine Humans Microglia Drug discovery Multiple sclerosis medicine.disease 3. Good health 10040 Clinic for Neurology Cytokine medicine.anatomical_structure 2728 Neurology (clinical) Neurology 2808 Neurology Neurology (clinical) Neuroscience Signal Transduction |
| Zdroj: | Multiple Sclerosis Journal |
| ISSN: | 1477-0970 1352-4585 |
| DOI: | 10.1177/1352458514543339 |
| Popis: | The pathogenesis of multiple sclerosis (MS) involves alterations to multiple pathways and processes, which represent a significant challenge for developing more-effective therapies. Systems biology approaches that study pathway dysregulation should offer benefits by integrating molecular networks and dynamic models with current biological knowledge for understanding disease heterogeneity and response to therapy. In MS, abnormalities have been identified in several cytokine-signaling pathways, as well as those of other immune receptors. Among the downstream molecules implicated are Jak/Stat, NF-Kb, ERK1/3, p38 or Jun/Fos. Together, these data suggest that MS is likely to be associated with abnormalities in apoptosis/cell death, microglia activation, blood-brain barrier functioning, immune responses, cytokine production, and/or oxidative stress, although which pathways contribute to the cascade of damage and can be modulated remains an open question. While current MS drugs target some of these pathways, others remain untouched. Here, we propose a pragmatic systems analysis approach that involves the large-scale extraction of processes and pathways relevant to MS. These data serve as a scaffold on which computational modeling can be performed to identify disease subgroups based on the contribution of different processes. Such an analysis, targeting these relevant MS-signaling pathways, offers the opportunity to accelerate the development of novel individual or combination therapies. |
| Databáze: | OpenAIRE |
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