Investigating the effects of taurine on Aβ-degradation proteins and neurogenesis-related genes in an LPS-induced neuroinflammatory SH-SY5Y cell model

Document Type : Original Article

Authors

1 Department of Biochemistry, North Tehran Branch, Islamic Azad University, Tehran, Iran

2 Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

3 Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): Taurine, a brain-abundant sulfonic acid, shows potential neuroprotective effects and may counter neurodegenerative processes. This study investigated the effects of taurine on neuroinflammation, focusing on Aβ-degrading proteins and gene expression related to neurogenesis in an LPS-stimulated SH-SY5Y cell model.
Materials and Methods: The effects of taurine (0.5 and 1 mg/ml) and LPS (0.5 and 10 μg/ml) on SH-SY5Y cell viability were assessed using the MTT assay. IL-1β and IL-6 expression was measured by real-time PCR, while matrix metalloproteinases (MMPs) and angiotensin-converting enzyme (ACE) levels were quantified via ELISA. Neurogenesis-related gene expression was evaluated using the Neurogenesis Plus RT² Profiler PCR array.
Results: The MTT assay results demonstrated that taurine treatment at concentrations of 0.5 and 1 mg/ml significantly attenuated the cytotoxicity induced by LPS stimulation in SH-SY5Y cells. Also, treatment with taurine significantly reduced the expression levels of the inflammatory genes IL-1β and IL-6 in LPS-stimulated SH-SY5Y cells (P<0.05). ELISA results further revealed that taurine treatment significantly increased the secretion levels of ACE and MMP-9 enzymes in LPS-stimulated SH-SY5Y cells (P<0.05). LPS exposure in SH-SY5Y cells significantly up-regulated genes related to apoptosis, cell migration, and synaptic function (P<0.005). Conversely, taurine treatment significantly increased the expression of genes involved in cell adhesion, synaptic function, growth factors, cytokines, differentiation, cell cycle, signaling, transcription, and cofactor activity (P<0.005).
Conclusion: These results suggest that taurine may act as a potential neuroprotective agent by increasing the secretion of MMP-9 and ACE, regulating neurogenesis-related genes, and reducing LPS-induced neuroinflammation.

Graphical Abstract

Investigating the effects of taurine on Aβ-degradation proteins and neurogenesis-related genes in an LPS-induced neuroinflammatory SH-SY5Y cell model

Keywords

Main Subjects

References

1. Si ZZ, Zou CJ, Mei X, Li XF, Luo H, Shen Y, et al. Targeting neuroinflammation in Alzheimer’s disease: From mechanisms to clinical applications. Neural Regen Res 2023; 18: 708-715. 
2. Xu J, Liu B, Shang G, Feng Z, Yang H, Chen Y, et al. Efficacy and safety of bilateral deep brain stimulation (DBS) for severe Alzheimer’s disease: A comparative analysis of fornix versus basal ganglia of meynert. CNS Neurosci Ther 2025; 31: e70285. 
3. Zhang J, Kong G, Yang J, Pang L, Li X. Pathological mechanisms and treatment progression of Alzheimer’s disease. Eur J Med Res 2025; 30:625. 
4. Krawczuk D, Kulczyńska-Przybik A, Mroczko B. The potential regulators of amyloidogenic pathway of APP processing in Alzheimer’s disease. Biomedicines. 2025; 13: 1513. 
5. Ullah R, Lee EJ. Advances in amyloid-β clearance in the brain and periphery: Implications for neurodegenerative diseases. Exp Neurobiol 2023; 32: 216. 
6. Cheng Y, Tian DY, Wang YJ. Peripheral clearance of brain-derived Aβ in Alzheimer’s disease: Pathophysiology and therapeutic perspectives. Transl Neurodegener 2020; 9: 1-1. 
7. Eckman EA, Watson M, Marlow L, Sambamurti K, Eckman CB. Alzheimer’s disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J Biol Chem 2003; 278: 2081-2084. 
8. Miners S, Ashby E, Baig S, Harrison R, Tayler H, Speedy E, et al. Angiotensin-converting enzyme levels and activity in Alzheimer’s disease: Differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res 2009; 1: 163. 
9. Loeffler DA. Experimental approaches for altering the expression of Abeta‐degrading enzymes. J Neurochem 2023;164: 725-763. 
10. Hofer HR, Tuan RS. Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies. Stem Cell Res Ther 2016; 7:131. 
11. Vardy ER, Catto AJ, Hooper NM. Proteolytic mechanisms in amyloid-β metabolism: Therapeutic implications for Alzheimer’s disease. Trends Mol Med 2005; 11: 464-472.
12. Sung PS, Lin PY, Liu CH, Su HC, Tsai KJ. Neuroinflammation and neurogenesis in Alzheimer’s disease and potential therapeutic approaches. Int J Mol Sci 2020; 21:701.
13. Gonzalez R, Reinberg D. The Notch pathway: A guardian of cell fate during neurogenesis. Curr Opin Cell Biol 2025; 95: 102543.
14. Tutukova S, Tarabykin V, Hernandez-Miranda LR. The role of neurod genes in brain development, function, and disease. Front Mol Neurosci 2021; 14: 662774.
15. Shademan B, Yousefi H, Sharafkhani R, Nourazarian A. LPS-induced neuroinflammation disrupts brain-derived neurotrophic factor and kinase pathways in Alzheimer’s disease cell models. Cell Mol Neurobiol 2025; 45: 102.
16. Ara Z, Rastogi D, Khan AA, Waliullah S. Beneficial effects: A review article. Acta Sci Med Sci 2022; 6: 95. 
17. Rossato RC, Granato AE, de Oliveira Moraes CD, Salles GN, Soares CP. Neuroprotective effects of taurine on SH-SY5Y cells under hydrocortisone induced stress. Res Soc Dev 2021; 10: e55510918426. 
18. Almohaimeed HM, Almars AI, Alsulaimani F, Basri AM, Althobaiti NA, Albalaw AE, et al. Investigating the potential neuroprotective benefits of taurine and Dihydrotestosterone and Hydroxyprogesterone levels in SH-SY5Y cells. Front Aging Neurosci 2024; 16: 1379431. 
19. Baliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, Spandidos DA, et al. Protective role of taurine against oxidative stress. Mol Med Rep 2021; 24: 1-9. 
20. Sharma S, Sahoo BM, Banik BK. Biological effects and mechanisms of taurine in various therapeutics. Curr Drug Discov Technol 2023; 20: 60-78. 
21. Li X, Bao X, Wang R. Neurogenesis-based epigenetic therapeutics for Alzheimer’s disease. Mol Med Rep 2016; 14: 1043-53. 
22. Subramanian VS, Teafatiller T, Agrawal A, Kitazawa M, Marchant JS. Effect of lipopolysaccharide and TNFα on neuronal ascorbic acid uptake. Mediators Inflamm 2021; 2021: 4157132.
23. Hasanpour M, Rahbarghazi R, Nourazarian A, Khaki-Khatibi F, Avci ÇB, Hassanpour M, et al. Conditioned medium from amniotic fluid mesenchymal stem cells could modulate Alzheimer’s disease-like changes in human neuroblastoma cell line SY-SY5Y in a paracrine manner. Tissue Cell 2022; 76: 101808.
24. Althobaiti NA, Alsharif I, Alhasani RH, Albalawi AE, Alshahrani MY, Almars AI, et al. Taurine and neuroprotection: A potential shield against methylglyoxal‐induced toxicity in SH‐SY5Y cells. J Biochem Mol Toxicol 2025; 39: e70343.
25. Al-Attabi A, Mukhlif BA, Al-Shami KR, Merza MS, Alkubaisy SA, Abdulhadi MA. Evaluation of the effect of taurine on the matrix metalloproteinase-9 and the expression changes of miRNA-21 and miRNA-146a in the SH-SY5Y cell line. Horm Mol Biol Clin Investig 2024; 45: 165-170.
26. Su Y, Fan W, Ma Z, Wen X, Wang W, Wu Q, et al. Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury. Neuroscience 2014; 266: 56-65.
27. Ni H, Han Y, Jin X. Celastrol inhibits colon cancer cell proliferation by downregulating miR-21 and PI3K/AKT/GSK-3β pathway. Int J Clin Exp Pathol 2019; 12: 808. 
28. Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 2012; 42: 2223-2232. 
29. Alkholifi FK, Albers DS. Attenuation of rotenone toxicity in SY5Y cells by taurine and N-acetyl cysteine alone or in combination. Brain Res 2015; 1622: 409-413. 
30. Erdem AY, Sevgili AM, Akbiyik F, Atilla PE, Cakar N, Balkanci ZD, et al. The effect of taurine on mesenteric blood flow and organ injury in sepsis. Amino Acids 2008; 35: 403-410. 
31. Nagl M, Hess MW, Pfaller K, Hengster P, Gottardi W. Bactericidal activity of micromolar N-chlorotaurine: evidence for its antimicrobial function in the human defense system. Antimicrob Agents Chemother 2000; 44: 2507-2513. 
32. Nam SY, Kim HM, Jeong HJ. The potential protective role of taurine against experimental allergic inflammation. Life Sci 2017; 184: 18-24. 
33. Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E, et al. Clearance systems in the brain—implications for Alzheimer disease. Nat Rev Neurol 2015;11:457.
34. Koronyo-Hamaoui M, Sheyn J, Hayden EY, Li S, Fuchs DT, Regis GC, et al. Peripherally derived angiotensin converting enzyme-enhanced macrophages alleviate Alzheimer-related disease. Brain 2020; 143: 336-358. 
35. Zhuang S, Wang HF, Wang X, Li J, Xing CM. The association of renin-angiotensin system blockade use with the risks of cognitive impairment of aging and Alzheimer’s disease: A meta-analysis. J Clin Neurosci 2016; 33: 32-38. 
36. Yin KJ, Cirrito JR, Yan P, Hu X, Xiao Q, Pan X, et al. Matrix metalloproteinases expressed by astrocytes mediate extracellular amyloid-β peptide catabolism. J Neurosci 2006; 26: 10939-10948. 
 
Iranian Journal of Basic Medical Sciences
Volume 29, Issue 7
July 2026
Pages 1043-1051

Files

Share

How to cite

Statistics