Full Length Research Article 

Retraction in process: Naringenin as a potent inhibitor molecule for targeting microtubule affinity-regulating kinase 4 (mark4): a molecular docking and in vitro study for therapeutics of Alzheimer's disease

Mohammad Zubair Alam^1,2*, Hala Abubaker Bagabir³, Mohammad Alameen Faisal Zaher⁴, Thamer M. A. Alqurashi⁵, Badrah S. Alghamdi^{1, 6}, Ghulam Md Ashraf^{1, 2}, Mohsin Kazi⁷

Adv. life sci., vol. 11, no. 1, pp. 136-143, February 2024
*^- Corresponding Author: Mohammad Zubair Alam (mohdzubairalam@yahoo.com)
Authors' Affiliations

 
[Date Received: 01/08/2023; Date Revised: 09/10/2023; Date Published: 25/02/2024]

Editorial Note: You are viewing the latest version of this manuscript having corrections in affiliations of authors and abstract sections, which are different from the original published copy.

Editorial Expression of Concern:

18 May 2025: Following publication of this paper, the internal audit (consequent to concerns on quality raised by Web of Science) notified Advancements in Life Sciences about problems in use of English language. By this Editorial Expression of Concern, we alert the scientific community of the errors as we reconcile the records.

Editorial Note:

28 May 2025: While reconciling the record of Turnitin originality analysis, 49% content of this article was found generated using AI tool/s without clear disclosure along with similarity on more than 4% with at least one source published prior to this article. 

Editorial board of Advancements in Life Sciences has started the process of retracting this article due to the above post-publication findings. The process shall be concluded after registering responses from the authors. Meanwhile, full text of the article shall remain unavailable for citations (this notice has been updated following insights derived from relevant COPE cases and the industry standards).

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Abstract
Introduction
Methods
Results
Discussion
References 

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Abstract

Background: The targeted inhibition of Microtubule Affinity-Regulating Kinase 4 (MARK4) using small molecule inhibitors has emerged as a promising therapeutic approach for diverse diseases, including neurological disorders such as Alzheimer’s disease. Ongoing research endeavors aim to develop novel and more effective MARK4 inhibitors with enhanced target specificity and reduced off-target effects. In the present study, we sought to investigate the binding affinity and impact of Naringenin on the activity of MARK4.

Methods: We employed a combination of molecular docking and other bioinformatics methods, a fluorescence-based inhibition assay, as well as a kinase activity assay to assess the binding affinity and inhibition potential of Naringenin against MARK4. Additionally, we utilized the MTT assay to examine the effect of Naringenin on the viability of two cell lines: the normal human cell line HEK-293 and the neuronal cell line SH-SY5Y. The IC₅₀ dose of Naringenin, determined from the MTT assay, provided a valuable reference point for subsequent neuronal cell line experiments.

Results: The results of the molecular docking demonstrated a robust binding affinity of Naringenin (-7.8 kcal/mol) to MARK4, affirming its potency as an inhibitor. Moreover, the fluorescence inhibition and kinase activity assays confirmed the inhibitory effect of Naringenin on MARK4. Interestingly, the MTT assay outcomes indicated that increasing concentrations of Naringenin did not significantly impact the viability of HEK 293 cells, while exhibiting a pronounced effect on SH-SY5Y neuronal cells. The IC₅₀ concentration of Naringenin was determined to be 10.0 ± 1.33 μM for SH-SY5Y neuronal cells.

Conclusion: In conclusion, this study reported Naringenin as a potential inhibitor molecule for MARK4, offering promising prospects for future therapeutic interventions in neuronal disorders specifically for Alzheimer’s disease.

Keywords: Inhibition; Microtubule Affinity-Regulating Kinase 4 (MARK4); Molecular docking; Naringenin; Neuronal disorders