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Relaxin-2 protects synaptic integrity via hippocampal NLRP3-mTOR-autophagy pathways in an age-dependent Alzheimer-like model Cover

Relaxin-2 protects synaptic integrity via hippocampal NLRP3-mTOR-autophagy pathways in an age-dependent Alzheimer-like model

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|Oct 2026
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References

  1. K. H. M. Chow and T. Abel, Neurodevelopmental origins of age-related neurodegenerative diseases, EBioMedicine 124 (2026) Article ID 106151 (12 pages); https://doi.org/10.1016/j.ebiom.2026.106151
  2. E. M. Planalp, R. E. Langhough, E. M. Jonaitis, C. A. Van Hulle, R. E. Wilson, G. Kollmorgen, C. Quijano-Rubio, O. C. Okonkwo, B. B. Bendlin, S. Asthana, K. Blennow, H. Zetterberg and S. C. Johnson, Synaptic markers are associated with cognitive decline after accounting for amyloid burden among an at-risk Alzheimer’s disease cohort, Sci. Rep. 15(1) (2025) Article ID 19399 (14 pages); https://doi.org/10.1038/s41598-025-04319-3
  3. S. E. J. Chee and E. Solito, The impact of ageing on the CNS immune response in Alzheimer’s disease, Front. Immunol. 12 (2021) Article ID 738511 (15 pages); https://doi.org/10.3389/fimmu.2021.738511
  4. G. Yang, X. Xu, W. Gao, X. Wang, Y. Zhao and Y. Xu, Microglia-orchestrated neuroinflammation and synaptic remodeling: Roles of pro-inflammatory cytokines and receptors in neurodegeneration, Front. Cell. Neurosci. 19 (2025) Article ID 1700692 (19 pages); https://doi.org/10.3389/fncel.2025.1700692
  5. S. E. Corcoran, R. Halai and M. A. Cooper, Pharmacological inhibition of the Nod-like receptor family pyrin domain containing 3 inflammasome with MCC950, Pharmacol. Rev. 73(3) (2021) 968–1000; https://doi.org/10.1124/pharmrev.120.000171
  6. N. Demirtas, B. S. Mazlumoglu and S. S. Palabiyik Yucelik, Role of NLRP3 inflammasomes in neurodegenerative diseases, Eurasian J. Med. 55(1) (2023) 98–105; https://doi.org/10.5152/eurasian-jmed.2023.23349
  7. J. Zerdka, P. Brasse, M. Piszka, E. Kwapien, M. Kubicka, J. Bartkowski, J. Banach, H. Dacyl and A. Owczarska, The mechanistic target of rapamycin (mTOR) pathway as a target of anti-aging therapies: The role of rapamycin and its analogs in the regulation of cellular processes and their impact on longevity, Cureus 17(12) (2025) Article ID e98514; https://doi.org/10.7759/cureus.98514
  8. J. M. Carosi, C. Fourrier, J. Bensalem and T. J. Sargeant, The mTOR-lysosome axis at the centre of ageing, FEBS Open Bio 12(4) (2022) 739–757; https://doi.org/10.1002/2211-5463.13347
  9. J. Q. Lu, H. Q. Wang, M. R. Fang, X. M. Ye and K. Y. Song, Autophagy-NLRP3 inflammasome crosstalk in microglia: A therapeutic target for multiple sclerosis, Inflammation 49(1) (2026) Article ID 23 (20 pages); https://doi.org/10.1007/s10753-025-02355-9
  10. A. Silvano, O. Ammar, A. Parenti, N. Strambi, V. Seravalli, D. Bani and M. Di Tommaso, Relationship between relaxin-2 levels in serum and mode of conception in twin gestations: A prospective cohort study, J. Obstet. Gynaecol. Res. 51 (2025) Article ID e16190 (7 pages); https://doi.org/10.1111/jog.16190
  11. N. Almeida-Pinto, T. B. Dschietzig, C. Bras-Silva and R. Adao, Cardiovascular effects of relaxin-2: Therapeutic potential and future perspectives, Clin. Res. Cardiol. 113(8) (2024) 1137–1150; https://doi.org/10.1007/s00392-023-02305-1
  12. A. Knezic, S. H. T. Truong, C. E. Moore, C. M. O. Barker, M. A. Hossain, C. S. Samuel and B. R. S. Broughton, The simultaneous targeting of RXFP1 and RXFP3 improves motor function and reduces brain inflammation, apoptosis and glial scarring following photothrombotic stroke in male mice, Biochem. Pharmacol. 243 (2026) Article ID (117523 (12 pages); https://doi.org/10.1016/j.bcp.2025.117523
  13. S. Nistri, C. Fiorillo, M. Becatti and D. Bani, Human relaxin-2 (Serelaxin) attenuates oxidative stress in cardiac muscle cells exposed in vitro to hypoxia-reoxygenation. Evidence for the involvement of reduced glutathione up-regulation, Antioxidants (Basel) 9(9) (2020) Article ID 774; https://doi.org/10.3390/antiox9090774
  14. F. Tapia Caceres, T. A. Gaspari, M. A. Hossain and C. S. Samuel, Relaxin inhibits the cardiac myofibroblast NLRP3 inflammasome as part of its anti-fibrotic actions via the angiotensin type 2 and ATP (P2X7) receptors, Int. J. Mol. Sci. 23(13) (2022) Article ID 7074 (22 pages); https://doi.org/10.3390/ijms23137074
  15. J. Liu, Y. Cai, K. U. Rahman, Q. Zhou, G. Liu, H. Kang, M. Li, S. Zhang, G. Wang, W. Feng, X. Zhang, G. Zhang, Y. Song and P. Li, Rh-relaxin-2 attenuates oxidative stress and neuronal apoptosis via ERK-nNOS-NO pathway after germinal matrix hemorrhage in rats, Fluids Barriers CNS 22(1) (2025) Article ID 8 (13 pages); https://doi.org/10.1186/s12987-024-00616-7
  16. J. H. Wang, H. B. Sheng and J. K. Li, Relaxin-2 ameliorates spinal cord injury by inhibiting micro-glia activation, Kaohsiung J. Med. Sci. 41(9) (2025) Article ID e70041 (9 pages); https://doi.org/10.1002/kjm2.70041
  17. A. J. S. Summerlee, D. J. Hornsby and D. G. Ramsey, The dipsogenic effects of rat relaxin: The effect of photoperiod and the potential role of relaxin on drinking in pregnancy, Endocrinology 139(5) (1998) 2322–2328; https://doi.org/10.1210/endo.139.5.5966
  18. Y. Fan, L. Du, Q. Fu, Z. Zhou, J. Zhang, G. Li and J. Wu, Inhibiting the NLRP3 inflammasome with MCC950 ameliorates isoflurane-induced pyroptosis and cognitive impairment in aged mice, Front. Cell. Neurosci. 12 (2018) Article ID 426 (9 pages); https://doi.org/10.3389/fncel.2018.00426
  19. A. Caccamo, S. Majumder, A. Richardson, R. Strong and S. Oddo, Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: Effects on cognitive impairments, J. Biol. Chem. 285 (2010) 13107–13120; https://doi.org/10.1074/jbc.M110.100420
  20. T. Liang, Y. Zhang, S. Wu, Q. Chen and L. Wang, The role of NLRP3 inflammasome in Alzheimer’s disease and potential therapeutic targets, Front. Pharmacol. 13 (2022) Article ID 845185 (21 pages); https://doi.org/10.3389/fphar.2022.845185
  21. G. Sita, A. Graziosi, P. Hrelia and F. Morroni, NLRP3 and infections: beta-amyloid in inflamma-some beyond neurodegeneration, Int. J. Mol. Sci. 22(13) (2021) Article ID 6984 (14 pages); https://doi.org/10.3390/ijms22136984
  22. W. Broszkiewicz and K. Dominska, The role of relaxins in blood cell modulation: interactions with relaxin family peptide receptor 1 (RXFP1) and glucocorticoid receptor (GR), Clin. Sci. (Lond) 139(21) (2025) 1431–1450; https://doi.org/10.1042/CS20256619
  23. K. M. Garner, R. Amin, R. W. Johnson, E. J. Scarlett and M. D. Burton, Microglia priming by inter-leukin-6 signaling is enhanced in aged mice, J. Neuroimmunol. 324 (2018) 90–99; https://doi.org/10.1016/j.jneuroim.2018.09.002
  24. S. Davoody, A. Asgari Taei, P. Khodabakhsh and L. Dargahi, mTOR signaling and Alzheimer’s disease: what we know and where we are?, CNS Neurosci. Ther. 30(4) (2024) Article ID (e14463 (17 pages); https://doi.org/10.1111/cns.14463
  25. A. Subramanian, T. Tamilanban, A. Alsayari, G. Ramachawolran, L. S. Wong, M. Sekar, S. H. Gan, V. Subramaniyan, S. V. Chinni, N. N. Izzati Mat Rani, N. Suryadevara and S. Wahab, Trilateral association of autophagy, mTOR and Alzheimer’s disease: potential pathway in the development for Alzheimer’s disease therapy, Front. Pharmacol. 13 (2022) Article ID 1094351 (15 pages); https://doi.org/10.3389/fphar.2022.1094351
  26. S. Ghosh Chowdhury, R. Ray and P. Karmakar, Relating aging and autophagy: A new perspective towards the welfare of human health, EXCLI J. 22 (2023) 732–748; https://doi.org/10.17179/excli2023-6300
  27. S. Lv, H. Liu and H. Wang, The interplay between autophagy and NLRP3 inflammasome in ischemia/reperfusion injury, Int. J. Mol. Sci. 22(16) (2021) Article ID 8773 (14 pages); https://doi.org/10.3390/ijms22168773
  28. R. Tenchov, J. M. Sasso, X. Wang and Q. A. Zhou, Aging hallmarks and progression and age-related diseases: A landscape view of research advancement, ACS Chem. Neurosci. 15(1) (2024) 1–30; https://doi.org/10.1021/acschemneuro.3c00531
  29. A. Azargoonjahromi, The duality of amyloid-beta: Its role in normal and Alzheimer’s disease states, Mol. Brain 17 (2024) Article ID 44 (24 pages); https://doi.org/10.1186/s13041-024-01118-1
  30. I. Bai, C. Keyser, Z. Zhang, B. Rosolia, J. Y. Hwang, R. S. Zukin and J. Yan, Epigenetic regulation of autophagy in neuroinflammation and synaptic plasticity, Front. Immunol. 15 (2024) Article ID 1322842 (13 pages); https://doi.org/10.3389/fimmu.2024.1322842
DOI: https://doi.org/10.2478/acph-2026-0023 | Journal eISSN: 1846-9558 | Journal ISSN: 1330-0075
Language: English
Accepted on: Sep 1, 2026
Published on: Oct 26, 2026
Published by: Croatian Pharmaceutical Society
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Related subjects:

© 2026 Daohe Wang, Zhigang Zhao, Yumei Ding, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.