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Direct Interaction of Minocycline to p47phox Contributes to its Attenuation of TNF-α-Mediated Neuronal PC12 Cell Death: Experimental and Simulation Validation

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Abstract

Kaempferol illustrates an example of attempting to discover new treatments for neurodegeneration by investigating the potential efficacy of natural products. Despite the identification of several molecular targets for this bio-active compound, the precise underlying pathways are not well elucidated yet. Recently, it has been shown through pulldown assay that kaemferol directly interacts with p47phox, the organizer subunit of NADPH oxidase-2 (NOX2) complex. Hence, in this study, we used homology modelling, computational docking, mutation analysis, molecular dynamics simulations and free energy calculations to determine how kaempferol interacts with p47phox. Firstly, 3D structure of p47phox was generated using x-ray structures of its domains. Then, it was docked with kaempferol, and finally 100-ns molecular dynamics (MD) simulations were performed and the global properties like root-mean square deviation (RMSD) and root-mean square fluctuations (RMSF) were calculated. Literature survey and computational analysis of key interacting amino acid residues of p47phox provided insights into a possible binding site for kaempferol, approximately around Trp193 and Cys196 located within the N–terminal SH3 domain of p47phox. Moreover, free energy calculations indicated that in silico substitution of Trp193 and Cys196 with arginine and alanine, respectively, results in less favorable interaction corroborating their importance in binding with kaempferol. Taken together, these findings suggest that kaempferol directly attaches to N–SH3 domain p47 phox, with a subsequent diminution of p47phox protein–protein interaction and possibly attenuation of NOX2 complex assembly, which reduces reactive oxygen species (ROS) generation. These observations will be beneficial for researchers exploring neuroprotection and for the development of p47phox inhibitors.

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References

  1. Szrok-Jurga, S., Turyn, J., Hebanowska, A., Swierczynski, J., Czumaj, A. & Sledzinski, T. et al. (2023). The role of Acyl-CoA β-oxidation in brain metabolism and neurodegenerative diseases. International Journal of Molecular Sciences, 24(18), 13977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. S. Hernandes, M., & Britto, L. R. (2012). NADPH oxidase and neurodegeneration. Current neuropharmacology, 10(4), 321–327

    Article  Google Scholar 

  3. Eid, S. A., Savelieff, M. G., Eid, A. A., & Feldman, E. L. (2022). Nox, Nox, are you there? The role of NADPH oxidases in the peripheral nervous system. Antioxidants & Redox Signaling, 37(7–9), 613–630

    Article  CAS  Google Scholar 

  4. Fang, J., Sheng, R. & Qin, Z. H. (2021). NADPH oxidases in the central nervous system: Regional and cellular localization and the possible link to brain diseases. Antioxidants & Redox Signaling, 35(12), 951–973

    Article  CAS  Google Scholar 

  5. Decourt, B., Lahiri, D. K. & Sabbagh, M. N. (2017). Targeting tumor necrosis factor alpha for Alzheimer’s disease. Current Alzheimer research, 14(4), 412–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Altenhofer, S., Radermacher, K. A., Kleikers, P. W., Wingler, K., & Schmidt, H. H. (2015). Evolution of NADPH oxidase inhibitors: Selectivity and mechanisms for target engagement. Antioxidants & redox signaling, 23(5), 406–427

    Article  Google Scholar 

  7. Rastogi, R., Geng, X., Li, F., & Ding, Y. (2016). NOX activation by subunit interaction and underlying mechanisms in disease. Frontiers in cellular neuroscience, 10, 301

    PubMed  Google Scholar 

  8. Karimi, G., Houee Levin, C., Dagher, M. C., Baciou, L., & Bizouarn, T. (2014). Assembly of phagocyte NADPH oxidase: A concerted binding process? Biochimica et biophysica acta, 1840(11), 3277–3283

    Article  CAS  PubMed  Google Scholar 

  9. Meijles, D. N., Fan, L. M., Howlin, B. J., & Li, J. M. (2014). Molecular insights of p47phox phosphorylation dynamics in the regulation of NADPH oxidase activation and superoxide production. The Journal of Biological Chemistry, 289, 22759–22770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Raad, H., Mouawia, H., Hassan, H., El-Seblani, M., Arabi-Derkawi, R., & Boussetta, T., et al. (2020). The protein kinase A negatively regulates reactive oxygen species production by phosphorylating gp91phox/NOX2 in human neutrophils. Free Radical Biology and Medicine, 160, 19–27

    Article  CAS  PubMed  Google Scholar 

  11. Dang, P. M., Stensballe, A., Boussetta, T., Raad, H., Dewas, C., Kroviarski, Y., Hayem, G., Jensen, O. N., Gougerot-Pocidalo, M. A., & El-Benna, J. (2006). A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. The Journal of Clinical Investigation, 116(7), 2033–2043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. El-Benna, J., Dang, P. M., Gougerot-Pocidalo, M. A., Marie, J. C. & Braut-Boucher, F. (2009). p47phox, the phagocyte NADPH oxidase/NOX2 organizer: structure, phosphorylation and implication in diseases. Experimental & Molecular Medicine, 41(4), 217–225

    Article  CAS  Google Scholar 

  13. Vermot, A., Petit-Härtlein, I., Smith, S. M. E., & Fieschi, F. (2021). NADPH oxidases (NOX): An overview from discovery, molecular mechanisms to physiology and pathology. Antioxidants, 10(6), 890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cifuentes-Pagano, E., Saha, J., Csanyi, G., Ghouleh, I. A., Sahoo, S., Rodriguez, A., Wipf, P., Pagano, P. J., & Skoda, E. M. (2013). Bridged tetrahydroisoquinolines as selective NADPH oxidase 2 (Nox2) inhibitors. MedChemComm, 4, 1085–1092

    Article  CAS  PubMed  Google Scholar 

  15. Dang, D. K., Shin, E. J., Nam, Y., Ryoo, S., Jeong, J. H., Jang, C. G., Nabeshima, T., Hong, J. S., & Kim, H. C. (2016). Apocynin prevents mitochondrial burdens, microglial activation, and pro-apoptosis induced by a toxic dose of methamphetamine in the striatum of mice via inhibition of p47phox activation by ERK. Journal of Neuroinflammation, 13, 12

    Article  PubMed  PubMed Central  Google Scholar 

  16. Mora-Pale, M., Kwon, S. J., Linhardt, R. J., & Dordick, J. S. (2012). Trimer hydroxylated quinone derived from apocynin targets cysteine residues of p47phox preventing the activation of human vascular NADPH oxidase. Free Radical Biology & Medicine, 52(5), 962–969

    Article  CAS  Google Scholar 

  17. Macias Perez M. E., Hernandez Rodriguez M., Cabrera Perez L. C., Fragoso-Vazquez M. J., Correa-Basurto J., Padilla M., II, Mendez Luna D., Mera Jimenez E., Flores Sandoval C., Tamay Cach F., Rosales-Hernandez M. C. (2017) Aromatic regions govern the recognition of NADPH oxidase inhibitors as diapocynin and its analogues, Archiv der Pharmazie, 350(10), 1700041

  18. Rezazadeh-Shojaee, F.-S., Ramazani, E., Kasaian, J., & Tayarani-Najaran, Z. (2022). Protective effects of 6-gingerol on 6-hydroxydopamine-induced apoptosis in PC12 cells through modulation of SAPK/JNK and survivin activation. Journal of Biochemical and Molecular Toxicology, 36(2), e22956

    Article  CAS  PubMed  Google Scholar 

  19. Gao, H. M., Zhou, H., & Hong, J. S. (2012). NADPH oxidases: Novel therapeutic targets for neurodegenerative diseases. Trends in Pharmacological Sciences, 33(6), 295–303

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hurkacz, M., Dobrek, L., & Wiela-Hojeńska, A. (2021). Antibiotics and the nervous system—which face of antibiotic therapy is real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)? Molecules, 26(24), 7456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Neha, & Parvez, S. (2023). Emerging therapeutics agents and recent advances in drug repurposing for Alzheimer’s disease. Ageing Research Reviews, 85, 101815

    Article  CAS  PubMed  Google Scholar 

  22. Garrido-Mesa, N., Zarzuelo, A., & Galvez, J. (2013). Minocycline: Far beyond an antibiotic. British Journal of Pharmacology, 169(2), 337–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Garrido-Mesa, N., Zarzuelo, A., & Galvez, J. (2013). What is behind the non-antibiotic properties of minocycline? Pharmacological Research, 67(1), 18–30

    Article  CAS  PubMed  Google Scholar 

  24. Li, C., Yuan, K., & Schluesener, H. (2013). Impact of minocycline on neurodegenerative diseases in rodents: a meta-analysis. Reviews in the Neurosciences, 24(5), 553–562

    Article  PubMed  Google Scholar 

  25. Daulatzai, M. A. (2016). Pharmacotherpy and Alzheimer’s disease: The M-drugs (melatonin, minocycline, modafinil, and memantine) approach. Current Pharmaceutical Design, 22(16), 2411–2430

    Article  CAS  PubMed  Google Scholar 

  26. Karachitos, A., Garcia Del Pozo, J. S., de Groot, P. W., Kmita, H., & Jordan, J. (2013). Minocycline mediated mitochondrial cytoprotection: premises for therapy of cerebrovascular and neurodegenerative diseases. Current Drug Targets, 14(1), 47–55

    Article  CAS  PubMed  Google Scholar 

  27. Garcez, M. L., Mina, F., Bellettini-Santos, T., Carneiro, F. G., Luz, A. P., Schiavo, G. L., Andrighetti, M. S., Scheid, M. G., Bolfe, R. P., & Budni, J. (2017). Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid beta (1-42) in mice. Progress in neuro-psychopharmacology & biological psychiatry, 77, 23–31

    Article  CAS  Google Scholar 

  28. Shultz, R. B., & Zhong, Y. (2017). Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury. Neural Regeneration Research, 12(5), 702–713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhu, S., Stavrovskaya, I. G., Drozda, M., Kim, B. Y., Ona, V., Li, M., Sarang, S., Liu, A. S., Hartley, D. M., Wu, D. C., Gullans, S., Ferrante, R. J., Przedborski, S., Kristal, B. S., & Friedlander, R. M. (2002). Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature, 417(6884), 74–78

    Article  CAS  PubMed  Google Scholar 

  30. Chen, M., Ona, V. O., Li, M., Ferrante, R. J., Fink, K. B., Zhu, S., Bian, J., Guo, L., Farrell, L. A., Hersch, S. M., Hobbs, W., Vonsattel, J. P., Cha, J. H., & Friedlander, R. M. (2000). Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nature Medicine, 6(7), 797–801

    Article  CAS  PubMed  Google Scholar 

  31. Xia, Z., & Friedlander, R. M. (2017). Minocycline in multiple sclerosis—compelling results but too early to tell. The New England Journal of Medicine, 376(22), 2191–2193

    Article  PubMed  Google Scholar 

  32. Sharifi, A. M., Eslami, H., Larijani, B., & Davoodi, J. (2009). Involvement of caspase-8, -9, and -3 in high glucose-induced apoptosis in PC12 cells. Neuroscience Letters, 459(2), 47–51.

    Article  CAS  PubMed  Google Scholar 

  33. Mansour, R. M., El Sayed, N. S., Ahmed, M. A. E., & El-Sahar, A. E. (2022). Addressing peroxisome proliferator-activated receptor-gamma in 3-nitropropionic acid-induced striatal neurotoxicity in rats. Molecular Neurobiology, 59(7), 4368–4383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Webb, B., & Sali, A. (2016). Comparative protein structure modeling using MODELLER. Current Protocols in Bioinformatics, 54, 5 6 1–5 6 37

    Article  PubMed  Google Scholar 

  35. Goodsell, D. S., Morris, G. M., & Olson, A. J. (1996). Automated docking of flexible ligands: Applications of AutoDock. Journal of Molecular Recognition, 9(1), 1–5

    Article  CAS  PubMed  Google Scholar 

  36. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., & Berendsen, H. J. (2005). GROMACS: fast, flexible, and free. Journal of Computational Chemistry, 26(16), 1701–1718

    Article  PubMed  Google Scholar 

  37. Haji-Allahverdipoor, K., Jalali Javaran, M., Rashidi Monfared, S., Khadem-Erfan, M. B., Nikkhoo, B., & Bahrami Rad, Z., et al. (2023). Insights into the effects of amino acid substitutions on the stability of reteplase structure: A molecular dynamics simulation study. Iran J Biotechnol, 21(1), e3175

    PubMed  PubMed Central  Google Scholar 

  38. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera–a visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612

    Article  CAS  PubMed  Google Scholar 

  39. Kumari, R., Kumar, R., C. Open Source Drug Discovery, & Lynn, A. (2014). g_mmpbsa–a GROMACS tool for high-throughput MM-PBSA calculations. Journal of Chemical Information and Modeling, 54(7), 1951–1962

    Article  CAS  PubMed  Google Scholar 

  40. Sato, Y., Fujimoto, S., Mukai, E., Sato, H., Tahara, Y., Ogura, K., Yamano, G., Ogura, M., Nagashima, K., & Inagaki, N. (2014). Palmitate induces reactive oxygen species production and beta-cell dysfunction by activating nicotinamide adenine dinucleotide phosphate oxidase through Src signaling. Journal of Diabetes Investigation, 5(1), 19–26

    Article  CAS  PubMed  Google Scholar 

  41. Amaral, M., Kokh, D. B., Bomke, J., Wegener, A., Buchstaller, H. P., Eggenweiler, H. M., Matias, P., Sirrenberg, C., Wade, R. C., & Frech, M. (2017). Protein conformational flexibility modulates kinetics and thermodynamics of drug binding. Nature Communications, 8(1), 2276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Giuliani, A. (2017). The application of principal component analysis to drug discovery and biomedical data. Drug Discovery Today, 22(7), 1069–1076

    Article  CAS  PubMed  Google Scholar 

  43. Wang L., Ran Zeng R., Qian Pang X., Gu Q., Tan W. (2015) The mechanisms of flavonoids inhibiting conformational transition of amyloid-β42 monomer: A comparative molecular dynamics simulation study. RSC Advances, 5(81), 66391–66402

  44. El-Benna, J., Dang, P. M., & Gougerot-Pocidalo, M. A. (2008). Priming of the neutrophil NADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane. Seminars in Immunopathology, 30(3), 279–289

    Article  CAS  PubMed  Google Scholar 

  45. Yamagishi, S., Yamada, M., Ishikawa, Y., Matsumoto, T., Ikeuchi, T., & Hatanaka, H. (2001). p38 mitogen-activated protein kinase regulates low potassium-induced c-Jun phosphorylation and apoptosis in cultured cerebellar granule neurons. The Journal of Biological Chemistry, 276(7), 5129–5133

    Article  CAS  PubMed  Google Scholar 

  46. Zhang, L., Xing, D., Liu, L., Gao, X., & Chen, M. (2007). TNFalpha induces apoptosis through JNK/Bax-dependent pathway in differentiated, but not naive PC12 cells. Cell Cycle, 6(12), 1479–1486

    Article  CAS  PubMed  Google Scholar 

  47. Brenner, D., Blaser, H., & Mak, T. W. (2015). Regulation of tumour necrosis factor signalling: Live or let die. Nature Reviews. Immunology, 15(6), 362–374

    Article  CAS  PubMed  Google Scholar 

  48. Cuadrado, A., & Nebreda, A. R. (2010). Mechanisms and functions of p38 MAPK signalling. The Biochemical Journal, 429(3), 403–417

    Article  CAS  PubMed  Google Scholar 

  49. Schrantz, N., Bourgeade, M. F., Mouhamad, S., Leca, G., Sharma, S., & Vazquez, A. (2001). p38-mediated regulation of an Fas-associated death domain protein-independent pathway leading to caspase-8 activation during TGFbeta-induced apoptosis in human Burkitt lymphoma B cells BL41. Molecular Biology of the Cell, 12(10), 3139–3151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fernandez-Gomez, F. J., Gomez-Lazaro, M., Pastor, D., Calvo, S., Aguirre, N., Galindo, M. F., & Jordan, J. (2005). Minocycline fails to protect cerebellar granular cell cultures against malonate-induced cell death. Neurobiology of Disease, 20(2), 384–391

    Article  CAS  PubMed  Google Scholar 

  51. Yong, V. W., Wells, J., Giuliani, F., Casha, S., Power, C., & Metz, L. M. (2004). The promise of minocycline in neurology. The Lancet. Neurology, 3(12), 744–751

    Article  PubMed  Google Scholar 

  52. Diguet, E., Gross, C. E., Tison, F., & Bezard, E. (2004). Rise and fall of minocycline in neuroprotection: need to promote publication of negative results. Experimental Neurology, 189(1), 1–4

    Article  CAS  PubMed  Google Scholar 

  53. Cheng, S., Hou, J., Zhang, C., Xu, C., Wang, L., Zou, X., Yu, H., Shi, Y., Yin, Z., & Chen, G. (2015). Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration. Scientific Reports, 5, 10535

    Article  PubMed  PubMed Central  Google Scholar 

  54. Scott, G., Zetterberg, H., Jolly, A., Cole, J. H., De Simoni, S., Jenkins, P. O., Feeney, C., Owen, D. R., Lingford-Hughes, A., Howes, O., Patel, M. C., Goldstone, A. P., Gunn, R. N., Blennow, K., Matthews, P. M., & Sharp, D. J. (2018). Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration. Brain : a Journal Of Neurology, 141(2), 459–471

    Article  PubMed  Google Scholar 

  55. Strahan, J. A., Walker, 2nd, W. H., Montgomery, T. R., & Forger, N. G. (2017). Minocycline causes widespread cell death and increases microglial labeling in the neonatal mouse brain. Developmental Neurobiology, 77(6), 753–766

    Article  CAS  PubMed  Google Scholar 

  56. Diguet, E., Fernagut, P. O., Wei, X., Du, Y., Rouland, R., Gross, C., Bezard, E., & Tison, F. (2004). Deleterious effects of minocycline in animal models of Parkinson’s disease and Huntington’s disease. The European Journal of Neuroscience, 19(12), 3266–3276

    Article  PubMed  Google Scholar 

  57. D.I. Huntington Study Group. (2010). A futility study of minocycline in Huntington’s disease, Movement disorders : official. Journal of the Movement Disorder Society, 25(13), 2219–2224

    Article  Google Scholar 

  58. Arnoux, I., Hoshiko, M., Sanz Diez, A., & Audinat, E. (2014). Paradoxical effects of minocycline in the developing mouse somatosensory cortex. Glia, 62(3), 399–410

    Article  PubMed  Google Scholar 

  59. Wei, X., Zhao, L., Liu, J., Dodel, R. C., Farlow, M. R., & Du, Y. (2005). Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation. Neuroscience, 131(2), 513–521

    Article  CAS  PubMed  Google Scholar 

  60. Guo, G., & Bhat, N. R. (2007). p38alpha MAP kinase mediates hypoxia-induced motor neuron cell death: A potential target of minocycline’s neuroprotective action. Neurochemical Research, 32(12), 2160–2166

    Article  CAS  PubMed  Google Scholar 

  61. El Benna, J., Han, J., Park, J. W., Schmid, E., Ulevitch, R. J., & Babior, B. M. (1996). Activation of p38 in stimulated human neutrophils: phosphorylation of the oxidase component p47phox by p38 and ERK but not by JNK. Archives of Biochemistry and Biophysics, 334(2), 395–400

    Article  CAS  PubMed  Google Scholar 

  62. Park, J. G., Yuk, Y., Rhim, H., Yi, S. Y., & Yoo, Y. S. (2002). Role of p38 MAPK in the regulation of apoptosis signaling induced by TNF-alpha in differentiated PC12 cells. Journal of Biochemistry and Molecular Biology, 35(3), 267–272

    CAS  PubMed  Google Scholar 

  63. Shao, X., Yang, X., Shen, J., Chen, S., Jiang, X., & Wang, Q., et al. (2020). TNF-α–induced p53 activation induces apoptosis in neurological injury. Journal of Cellular and Molecular Medicine, 24, 6796–6803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. El-Benna, J., Hurtado-Nedelec, M., Marzaioli, V., Marie, J. C., Gougerot-Pocidalo, M. A., & Dang, P. M. (2016). Priming of the neutrophil respiratory burst: Role in host defense and inflammation. Immunological Reviews, 273(1), 180–193

    Article  CAS  PubMed  Google Scholar 

  65. Sumimoto, H., Hata, K., Mizuki, K., Ito, T., Kage, Y., Sakaki, Y., Fukumaki, Y., Nakamura, M., & Takeshige, K. (1996). Assembly and activation of the phagocyte NADPH oxidase. Specific interaction of the N-terminal Src homology 3 domain of p47phox with p22phox is required to activate the NADPH oxidase. The Journal of Biological Chemistry, 271(36), 22152–22158

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the Neuroscience Research Center and Neuropharmacology Institute for providing access to their research facilities. This work was supported by the research council of the Kerman University of Medical Sciences, Kerman, Iran. Also, we appreciate the Faculty of Pharmacy, Hormozgan University of Medicinal Sciences, for providing the supercomputing service.

Funding

Financial support for this study was provided by the research council of the Kerman University of Medical Sciences, Kerman, Iran. The funding facilitated various aspects of the research, including data collection, analysis, and interpretation.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medicinal Sciences, Bandar Abbas, Iran

    Habib Eslami

  2. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Koosha Rokhzadi & Kaveh Haji-Allahverdipoor

  3. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Mohsen Basiri & Saeed Esmaeili-Mahani

  4. Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

    Zahra Mahmoodi

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Contributions

Habib Eslami and Kaveh Haji-Allahverdipoor led the conception, design, and coordination of the study, overseeing data collection and conducting experiments and simulation validation. Kaveh Haji-Allahverdipoor also served as the supervisor for the computational process and simulation validation. Koosha Rokhzadi operated in the simulation validation (computational process) and was involved in manuscript preparation and editing. Mohsen Basiri, Saeed Esmaeili-Mahani, and Zahra Mahmoodi contributed to data analysis, interpretation, and overall project management for manuscript preparation. Kaveh Haji-Allahverdipoor assisted in data collection, conducted the literature review, and played a significant role in manuscript revision. All authors reviewed and approved the final version of the manuscript.

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Correspondence to Kaveh Haji-Allahverdipoor.

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Eslami, H., Rokhzadi, K., Basiri, M. et al. Direct Interaction of Minocycline to p47phox Contributes to its Attenuation of TNF-α-Mediated Neuronal PC12 Cell Death: Experimental and Simulation Validation. Cell Biochem Biophys (2024). https://doi.org/10.1007/s12013-024-01279-9

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