MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease

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dc.contributor.authorWaseem, Rashid
dc.contributor.authorAnwar, Saleha
dc.contributor.authorKhan, Shama
dc.contributor.authorShamsi, Anas
dc.contributor.authorHassan, Md. Imtaiyaz
dc.contributor.authorAnjum, Farah
dc.contributor.authorShafie, Alaa
dc.contributor.authorIslam, Asimul
dc.contributor.authorYadav, Dharmendra Kumar
dc.date.accessioned2021-10-25T11:04:17Z
dc.date.available2021-10-25T11:04:17Z
dc.date.issued2021-10-12
dc.date.updated2021-10-22T13:55:47Z
dc.description.abstractIrisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (<i>K</i> = 0.8 × 10<sup>7</sup> M<sup>−1</sup>), subsequently inhibiting its activity (IC<sub>50</sub> = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases.en_US
dc.identifier10.3390/ijms222010986
dc.identifier.apacitationWaseem, R., Anwar, S., Khan, S., Shamsi, A., Hassan, Md. Imtaiyaz., Anjum, F., ... Yadav, D. K. (2021). MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease. <i>International Journal of Molecular Sciences</i>, 22(20), 10986. http://hdl.handle.net/11427/35286en_ZA
dc.identifier.chicagocitationWaseem, Rashid, Saleha Anwar, Shama Khan, Anas Shamsi, Md. Imtaiyaz Hassan, Farah Anjum, Alaa Shafie, Asimul Islam, and Dharmendra Kumar Yadav "MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease." <i>International Journal of Molecular Sciences</i> 22, 20. (2021): 10986. http://hdl.handle.net/11427/35286en_ZA
dc.identifier.citationWaseem, R., Anwar, S., Khan, S., Shamsi, A., Hassan, Md. Imtaiyaz., Anjum, F., Shafie, A. & Islam, A. et al. 2021. MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease. <i>International Journal of Molecular Sciences.</i> 22(20):10986. http://hdl.handle.net/11427/35286en_ZA
dc.identifier.ris TY - Journal Article AU - Waseem, Rashid AU - Anwar, Saleha AU - Khan, Shama AU - Shamsi, Anas AU - Hassan, Md. Imtaiyaz AU - Anjum, Farah AU - Shafie, Alaa AU - Islam, Asimul AU - Yadav, Dharmendra Kumar AB - Irisin is a clinically significant protein playing a valuable role in regulating various diseases. Irisin attenuates synaptic and memory dysfunction, highlighting its importance in Alzheimer’s disease. On the other hand, Microtubule Affinity Regulating Kinase 4 (MARK4) is associated with various cancer types, uncontrolled neuronal migrations, and disrupted microtubule dynamics. In addition, MARK4 has been explored as a potential drug target for cancer and Alzheimer’s disease therapy. Here, we studied the binding and subsequent inhibition of MARK4 by irisin. Irisin binds to MARK4 with an admirable affinity (<i>K</i> = 0.8 × 10<sup>7</sup> M<sup>−1</sup>), subsequently inhibiting its activity (IC<sub>50</sub> = 2.71 µm). In vitro studies were further validated by docking and simulations. Molecular docking revealed several hydrogen bonds between irisin and MARK4, including critical residues, Lys38, Val40, and Ser134. Furthermore, the molecular dynamic simulation showed that the binding of irisin resulted in enhanced stability of MARK4. This study provides a rationale to use irisin as a therapeutic agent to treat MARK4-associated diseases. DA - 2021-10-12 DB - OpenUCT DP - University of Cape Town IS - 20 J1 - International Journal of Molecular Sciences LK - https://open.uct.ac.za PY - 2021 T1 - MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease TI - MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease UR - http://hdl.handle.net/11427/35286 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35286
dc.identifier.vancouvercitationWaseem R, Anwar S, Khan S, Shamsi A, Hassan Md Imtaiyaz, Anjum F, et al. MAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Disease. International Journal of Molecular Sciences. 2021;22(20):10986. http://hdl.handle.net/11427/35286.en_ZA
dc.language.isoenen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceInternational Journal of Molecular Sciencesen_US
dc.source.journalissue20en_US
dc.source.journalvolume22en_US
dc.source.pagination10986en_US
dc.source.urihttps://www.mdpi.com/journal/ijms
dc.source.urihttps://www.mdpi.com/journal/ijms
dc.titleMAP/Microtubule Affinity Regulating Kinase 4 Inhibitory Potential of Irisin: A New Therapeutic Strategy to Combat Cancer and Alzheimer’s Diseaseen_US
dc.typeJournal Articleen_US
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