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      Network pharmacology drug repurposing strategy for neurovascular diseases

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            Abstract

            Stroke is currently the third cause of death and first of disability in industrialized countries. However, translational stroke research has yielded only one thrombolytic and no neuroprotective therapy over the last decades. In fact, only single-drug targets were hitherto pursued leading to no patient benefit and thus obstructing innovation in the most profound manner. Contrary, we now know that complex diseases are defined by multitarget modules of dysregulated genes causing different pathophysiological scenarios. Therefore, we now propose an in silico-based multitarget approach based on human disease genes linked to further identify mechanistically-related potential targets which could be then pharmacologically modulated following a network pharmacology therapeutic approach. Indeed, network pharmacology exploits this concept by simultaneously targeting several components of a disease module, combining mechanistically related and therefore synergistic drugs. This (i) allows to reduce the dose of each drug, (ii) thereby decreases potential side-effects, and (iii) through synergy enhances the full therapeutic effect. Additionally, to maximally speed-up market entry, we aim to follow a drug repurposing strategy which ensures therapeutic safety and quick access to the pharmaceutic market. Altogether, we propose a mechanism-based therapy targeting the underlying cause of the disease being modulated by a safe, easily translational therapeutic approach for patient suffering from neurovascular diseases.

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            Author and article information

            Conference
            ScienceOpen
            25 July 2022
            Affiliations
            [1 ] Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany
            [2 ] Department of Pharmacology and Personalised Medicine, School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
            [3 ] Institute of Computational Systems Biology, University of Hamburg, Hamburg, Germany
            [4 ] School of Computing Science, Newcastle University, United Kingdom
            Author notes
            Author information
            https://orcid.org/0000-0002-0935-074X
            Article
            10.14293/S2199-1006.1.SOR-.PPPVKQDY.v1
            580be6b8-5f2b-4c36-8ad7-d4bee2ec6c4f

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            RExPO22
            Maastricht, Netherlands
            2-3 September, 2022
            History
            : 25 July 2022

            The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
            network pharmacology,drug repurposing,systems medicine,Stroke

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