Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings

Dilek Karataş; Tugce Karaduman Yesıldal

doi:10.29002/asujse.1881741

EN TR

Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings

Öz

The increasing intensity of environmental and industrial activities worldwide has led to elevated exposure to heavy metals, representing a significant environmental problem affecting human health. Heavy metals such as lead, mercury, arsenic, and cadmium can cross the blood–brain barrier and accumulate in the central nervous system, where they induce neurotoxic effects. These effects are mediated by multiple interrelated mechanisms, including oxidative stress, mitochondrial dysfunction, disruption of calcium homeostasis, and sustained neuroinflammatory responses. Such mechanisms are known to contribute to the pathogenesis of several neurodegenerative disorders, particularly Alzheimer’s and Parkinson’s diseases. The limited efficacy of current therapeutic approaches has increased interest in alternative and multi-target treatment strategies. In this context, rifampicin, a well-established antibiotic used in tuberculosis therapy, has been reported to exhibit antioxidant, anti-inflammatory, and autophagy-related effects beyond its antimicrobial activity. This review summarizes current knowledge on the molecular mechanisms of heavy metal–induced neurotoxicity and discusses the potential neuroprotective role of rifampicin based on available experimental and clinical evidence.

Anahtar Kelimeler

Ağır Metal Kaynaklı Nörotoksisitenin Moleküler Temelleri ve Rifampisinin Nöroprotektif Rolü: Güncel Bulguların Derlenmesi

Öz

Dünya’da çevresel ve endüstriyel faaliyetlerin artmasıyla birlikte ağır metallere maruziyet, merkezi sinir sistemi üzerinde ciddi toksik etkiler oluşturan önemli bir çevresel sorun haline gelmiştir. Kurşun, civa, arsenik ve kadmiyum gibi ağır metaller kan-beyin bariyerini aşarak beyinde birikmekte; oksidatif stres, mitokondriyal disfonksiyon, kalsiyum homeostazının bozulması ve kronik nöroinflamasyon gibi birbiriyle ilişkili mekanizmalar yoluyla nörotoksisiteye neden olmaktadır. Bu süreçler, Alzheimer ve Parkinson hastalığı başta olmak üzere çeşitli nörodejeneratif hastalıkların patogenezi ile yakından ilişkilidir. Mevcut tedavi yaklaşımlarının sınırlı etkinliği, çok hedefli ve yeni terapötik stratejilere olan ihtiyacı artırmıştır. Bu bağlamda, tüberküloz tedavisinde uzun yıllardır kullanılan rifampisinin; antioksidan, anti-inflamatuar ve otofaji düzenleyici özellikleri sayesinde potansiyel bir nöroprotektif ajan olabileceği bildirilmektedir. Bu derleme, ağır metal kaynaklı nörotoksisitenin moleküler temellerini ve rifampisinin olası nöroprotektif etkilerini güncel literatür ışığında bütüncül bir bakış açısıyla değerlendirmeyi amaçlamaktadır.

Anahtar Kelimeler

Kaynakça

Jaishankar, M., Tseten, T., Anbalagan, N., Mathew, B. B., & Beeregowda, K. N. (2014). Toxicity, mechanism and health effects of some heavy metals. Interdisciplinary Toxicology, 7(2), 60–72. https://doi.org/10.2478/intox-2014-0009
Singh, N., Kumar, A., Gupta, V. K., & Sharma, B. (2018). Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chemical Research in Toxicology, 31(10), 1009–1021. https://doi.org/10.1021/acs.chemrestox.8b00193
Li, Y.-L., Huang, Z.-X., Peng, J., Ho, T.-T., Huang, H., Aschner, M., & Jiang, Y.-M. (2026). Advances in understanding the neurotoxicity of lead, cadmium, arsenic, and therapeutic strategies. Toxicology Letters, 415, 111810. https://doi.org/10.1016/j.toxlet.2025.111810
Yu, J., Chen, Z., Gao, W., He, S., Xiao, D., Fan, W., Huo, M., & Nugroho, W. A. (2025). Global trends and prospects in research on heavy metal pollution at contaminated sites. Journal of Environmental Management, 383, 125402. https://doi.org/10.1016/j.jenvman.2025.125402
Calderón-Garcidueñas, L., & Villarreal-Ríos, R. (2017). Living close to heavy traffic roads, air pollution, and dementia. The Lancet, 389(10070), 675–677. https://doi.org/10.1016/S0140-6736(16)32596-X
Khatri, D. K., Kadbhane, A., Patel, M., Nene, S., Atmakuri, S., Srivastava, S., & Singh, S. B. (2021). Gauging the role and impact of drug interactions and repurposing in neurodegenerative disorders. Current Research in Pharmacology and Drug Discovery, 2, 100022. https://doi.org/10.1016/j.crphar.2021.100022
Balali-Mood, M., Naseri, K., Tahergorabi, Z., Khazdair, M. R., & Sadeghi, M. (2021). Toxic mechanisms of five heavy metals: Mercury, lead, chromium, cadmium, and arsenic. Frontiers in Pharmacology, 12, 643972. https://doi.org/10.3389/fphar.2021.643972
Nie, J., Wen, L., Lai, Z., Lin, C., Li, H., Zhang, J., Xie, S., Ben, X., & Jing, C. (2025). The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: An unsupervised clustering approach. Frontiers in Public Health, 13, 1516879. https://doi.org/10.3389/fpubh.2025.1516879

Chin-Chan, M., Navarro-Yepes, J., & Quintanilla-Vega, B. (2015). Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Frontiers in Cellular Neuroscience, 9, 124. https://doi.org/10.3389/fncel.2015.00124
Deavall, D. G., Martin, E. A., Horner, J. M., & Roberts, R. (2012). Drug-induced oxidative stress and toxicity. Journal of Toxicology, 2012, 645460. https://doi.org/10.1155/2012/645460
Harrison, J. F. (2005). Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance. Nucleic Acids Research, 33(14), 4660–4671. https://doi.org/10.1093/nar/gki759
Das, S., Murumulla, L., Ghosh, P., & Challa, S. (2025). Heavy metal-induced disruption of the autophagy-lysosomal pathway: İmplications for aging and neurodegenerative disorders. BioMetals, 38(2), 371–417. https://doi.org/10.1007/s10534-025-00665-x
Nowicka, B. (2022). Heavy metal–induced stress in eukaryotic algae—mechanisms of heavy metal toxicity and tolerance with particular emphasis on oxidative stress in exposed cells and the role of antioxidant response. Environmental Science and Pollution Research, 29(12), 16860–16911. https://doi.org/10.1007/s11356-021-18419-w
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021). From combinations to multitarget‐directed ligands: A continuum in Alzheimer’s disease polypharmacology. Medicinal Research Reviews, 41(5), 2606–2633. https://doi.org/10.1002/med.21699
Jalencas, X., & Mestres, J. (2013). On the origins of drug polypharmacology. MedChemComm, 4(1), 80–87. https://doi.org/10.1039/C2MD20242E
Reddy, A. S., & Zhang, S. (2013). Polypharmacology: Drug discovery for the future. Expert Review of Clinical Pharmacology, 6(1), 41–47. https://doi.org/10.1586/ecp.12.74
Acuña, L., Hamadat, S., Corbalán, N. S., González-Lizárraga, F., dos-Santos-Pereira, M., Rocca, J., Sepúlveda Díaz, J., Del-Bel, E., Papy-García, D., Chehín, R. N., Michel, P. P., & Raisman-Vozari, R. (2019). Rifampicin and its derivative rifampicin quinone reduce microglial inflammatory responses and neurodegeneration induced in vitro by α-synuclein fibrillary aggregates. Cells, 8(8), 776. https://doi.org/10.3390/cells8080776
Vaezipour, N., Bigi, S., Song, R., & Ritz, N. (2025). Rifampicin and its neuroprotective properties in humans – A systematic review. Biomedicine & Pharmacotherapy, 185, 117928. https://doi.org/10.1016/j.biopha.2025.117928
Ahmed, G., Rahaman, M. S., Perez, E., & Khan, K. M. (2025). Associations of environmental exposure to arsenic, manganese, lead, and cadmium with Alzheimer’s disease: A review of recent evidence from mechanistic studies. Journal of Xenobiotics, 15(2), 47. https://doi.org/10.3390/jox15020047
Tyczyńska, M., Gędek, M., Brachet, A., Stręk, W., Flieger, J., Teresiński, G., & Baj, J. (2024). Trace elements in Alzheimer’s disease and dementia: The current state of knowledge. Journal of Clinical Medicine, 13(8), 2381. https://doi.org/10.3390/jcm13082381
Cheng, Y., Zhao, Y., Chen, C., & Zhang, F. (2026). Metallothionein and neurodegenerative diseases. Neural Regeneration Research, 21, ArticleinPress. https://doi.org/10.4103/NRR.NRR-D-25-00011
Chen, L., Xu, B., Liu, L., Luo, Y., Zhou, H., Chen, W., Shen, T., Han, X., Kontos, C. D., & Huang, S. (2011). Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radical Biology and Medicine, 50(5), 624–632. https://doi.org/10.1016/j.freeradbiomed.2010.12.032
Yusoff, N. S. N., Knight, V. F., Shakrin, N. N. S. M., & Yunus, W. M. Z. W. (2025). Heavy metal toxicity and its treatment. Advances in Human Biology, 15(1), 30–46. https://doi.org/10.4103/aihb.aihb_70_24
Koyama, H., Kamogashira, T., & Yamasoba, T. (2024). Heavy metal exposure: Molecular pathways, clinical implications, and protective strategies. Antioxidants, 13(1), 76. https://doi.org/10.3390/antiox13010076
Fatima, G., Raza, A. M., & Dhole, P. (2026). Heavy metal exposure and its health implications: A comprehensive review. Indian Journal of Clinical Biochemistry, 41(2), 152–180. https://doi.org/10.1007/s12291-025-01322-3
Flora, S. J. S. (2009). Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxidative Medicine and Cellular Longevity, 2(4), 191–206. https://doi.org/10.4161/oxim.2.4.9112
Xie, C., Wu, N., Guo, J., Ma, L., & Zhang, C. (2025). The key role of the ferroptosis mechanism in neurological diseases and prospects for targeted therapy. Frontiers in Neuroscience, 19, 1591417. https://doi.org/10.3389/fnins.2025.1591417
Jiang, T., Ma, W., Dong, W., Zhou, H., & Mao, X. (2025). Ferroptosis-associated transcriptional factors in neurological diseases: Molecular mechanisms and therapeutic prospects. Experimental & Molecular Medicine, 57(12), 2763–2781. https://doi.org/10.1038/s12276-025-01611-0
Cassera, E., Ferrari, E., Vignati, D. A. L., & Capucciati, A. (2025). The interaction between metals and catecholamines: Oxidative stress, DNA damage, and implications for human health. Brain Research Bulletin, 226, 111366. https://doi.org/10.1016/j.brainresbull.2025.111366
Wang, Y., Zhou, J., Zhou, Q., & Wang, H. (2025). New progress on the role and mechanism of tau protein in Alzheimer’s disease and depression. Frontiers in Neurology, 16, 1551273. https://doi.org/10.3389/fneur.2025.1551273
Jomova, K., Alomar, S. Y., Nepovimova, E., Kuca, K., & Valko, M. (2025). Heavy metals: Toxicity and human health effects. Archives of Toxicology, 99(1), 153–209. https://doi.org/10.1007/s00204-024-03903-2
Thakur, M., Rachamalla, M., Niyogi, S., Datusalia, A. K., & Flora, S. J. S. (2021). Molecular mechanism of arsenic-induced neurotoxicity including neuronal dysfunctions. International Journal of Molecular Sciences, 22(18), 10077. https://doi.org/10.3390/ijms221810077
Raha, S., & Robinson, B. H. (2000). Mitochondria, oxygen free radicals, disease and ageing. Trends in Biochemical Sciences, 25(10), 502–508. https://doi.org/10.1016/S0968-0004(00)01674-1
Pieńkowska, N., Fahnestock, M., Mahadeo, C., Zaborniak, I., Chmielarz, P., Bartosz, G., & Sadowska-Bartosz, I. (2022). Induction of oxidative stress in SH-SY5Y cells by overexpression of hTau40 and its mitigation by redox-active nanoparticles. International Journal of Molecular Sciences, 24(1), 359. https://doi.org/10.3390/ijms24010359
Aygörmez, S., Dalkılınç, E., Akaras, N., & Maraşlı, Ş. (2025). Effects of morin against tetracycline-induced liver injury in rats by biochemical and histopathological methods. Journal of Advances in VetBio Science and Techniques, 10(3), 153–161. https://doi.org/10.31797/vetbio.1696205
ames, A. S., Ugwor, E. I., Akamo, A. J., Akinloye, D. I., Kosoko, A. M., Olagunju, B. A., Ezenandu, E. O., Amaogu, C. C., Adebiyi, V., Thomas, F. C., & Ugbaja, R. N. (2025). Palmitic acid-induced renal injury: Unravelling the molecular mechanisms and the protective role of lycopene. Cell Biochemistry and Biophysics, 83(4), 4001–4013. https://doi.org/10.1007/s12013-025-01775-6
Cheng, H., Yang, B., Ke, T., Li, S., Yang, X., Aschner, M., & Chen, P. (2021). Mechanisms of metal-induced mitochondrial dysfunction in neurological disorders. Toxics, 9(6), 142. https://doi.org/10.3390/toxics9060142
Smith, E. F., Shaw, P. J., & De Vos, K. J. (2019). The role of mitochondria in amyotrophic lateral sclerosis. Neuroscience Letters, 710, 132933. https://doi.org/10.1016/j.neulet.2017.06.052
Cadonic, C., Sabbir, M. G., & Albensi, B. C. (2016). Mechanisms of mitochondrial dysfunction in Alzheimer’s disease. Molecular Neurobiology, 53(9), 6078–6090. https://doi.org/10.1007/s12035-015-9515-5
Correia-Melo, C., & Passos, J. F. (2015). Mitochondria: Are they causal players in cellular senescence? Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1847(11), 1373–1379. https://doi.org/10.1016/j.bbabio.2015.05.017
Gogia, N., & Kumar, P. (2025). Mercury poisoning: Effects on the central nervous system. In Heavy Metal Toxicity and Neurodegeneration (pp. 55–76). Elsevier. https://doi.org/10.1016/B978-0-443-36575-1.00014-5
Hirsch, E. C., & Hunot, S. (2009). Neuroinflammation in Parkinson’s disease: A target for neuroprotection? The Lancet Neurology, 8(4), 382–397. https://doi.org/10.1016/S1474-4422(09)70062-6
Acuna, L., Corbalán, N., & Raisman-Vozari, R. (2020). Rifampicin quinone pretreatment improves neuronal survival by modulating microglia inflammation induced by α-synuclein. Neural Regeneration Research, 15(8), 1473–1474. https://doi.org/10.4103/1673-5374.274336
dos‐Santos‐Pereira, M., Acuña, L., Hamadat, S., Rocca, J., González‐Lizárraga, F., Chehín, R., Sepulveda‐Diaz, J., Del‐Bel, E., Raisman‐Vozari, R., & Michel, P. P. (2018). Microglial glutamate release evoked by α‐synuclein aggregates is prevented by dopamine. Glia, 66(11), 2353–2365. https://doi.org/10.1002/glia.23472
Rizzuto, R., De Stefani, D., Raffaello, A., & Mammucari, C. (2012). Mitochondria as sensors and regulators of calcium signalling. Nature Reviews Molecular Cell Biology, 13(9), 566–578. https://doi.org/10.1038/nrm3412
Branca, J. J. V., Fiorillo, C., Carrino, D., Paternostro, F., Taddei, N., Gulisano, M., Pacini, A., & Becatti, M. (2020). Cadmium-induced oxidative stress: Focus on the central nervous system. Antioxidants, 9(6), 492. https://doi.org/10.3390/antiox9060492
Qu, W., Yan, G., Du, Y., Zhou, X., Huang, C., Li, B., Zhou, J., & Li, Q. (2025). Crosstalk between mitochondrial DNA and immune response: Focus on autism spectrum disorder. Molecular Neurobiology, 62(5), 5629–5639. https://doi.org/10.1007/s12035-024-04637-z
Son, Y.-O., Hitron, J. A., Wang, X., Chang, Q., Pan, J., Zhang, Z., Liu, J., Wang, S., Lee, J.-C., & Shi, X. (2010). Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells. Toxicology and Applied Pharmacology, 245(2), 226–235. https://doi.org/10.1016/j.taap.2010.03.004
Cronican, A. A., Fitz, N. F., Carter, A., Saleem, M., Shiva, S., Barchowsky, A., Koldamova, R., Schug, J., & Lefterov, I. (2013). Genome-wide alteration of histone H3K9 acetylation pattern in mouse offspring prenatally exposed to arsenic. PLoS ONE, 8(2), e53478. https://doi.org/10.1371/journal.pone.0053478
Zhou, R., Zhao, J., Li, D., Chen, Y., Xiao, Y., Fan, A., Chen, X.-T., & Wang, H.-L. (2020). Combined exposure of lead and cadmium leads to the aggravated neurotoxicity through regulating the expression of histone deacetylase 2. Chemosphere, 252, 126589. https://doi.org/10.1016/j.chemosphere.2020.126589
Barcia-Sanjurjo, I., Vázquez-Cedeira, M., Barcia, R., & Lazo, P. A. (2013). Sensitivity of the kinase activity of human vaccinia-related kinase proteins to toxic metals. JBIC Journal of Biological Inorganic Chemistry, 18(4), 473–482. https://doi.org/10.1007/s00775-013-0992-6
Guevara-Ramírez, P., Tamayo-Trujillo, R., Cadena-Ullauri, S., Ruiz-Pozo, V., Paz-Cruz, E., Annunziata, G., Verde, L., Frias-Toral, E., Simancas-Racines, D., & Zambrano, A. K. (2024). Heavy metals in the diet: Unraveling the molecular pathways linked to neurodegenerative disease risk. Food and Agricultural Immunology, 35(1), 2434457. https://doi.org/10.1080/09540105.2024.2434457
Rashid, F., Khan, K. M., Saiprakash, S., Ahmed, G., Sultana, R., Parvez, F., Islam, Z., & Rahaman, M. S. (2025). Epidemiological evidence on the associations of metal exposure with Alzheimer’s disease and related dementias among elderly women. Journal of Clinical Medicine, 14(11), 3776. https://doi.org/10.3390/jcm14113776
Althobaiti, N. A. (2025). Heavy metals exposure and Alzheimer’s disease: Underlying mechanisms and advancing therapeutic approaches. Behavioural Brain Research, 476, 115212. https://doi.org/10.1016/j.bbr.2024.115212
Kulcsárová, K., Piel, J. H. A., & Schaeffer, E. (2025). Environmental toxins in neurodegeneration - A narrative review. Neurological Research and Practice, 7(1), 93. https://doi.org/10.1186/s42466-025-00452-6
Beloor Suresh, A., Rosani, A., Patel, P., & Wadhwa, R. (2025). Rifampin. In Encyclopedia of Toxicology, Fourth Edition: Volume 1-9. StatPearls Publishing. https://doi.org/10.1016/B978-0-12-824315-2.00695-3
Kora, R., Brodsky, S. V., Nadasdy, T., Agra, D., & Satoskar, A. A. (2018). Rifampicin in nontuberculous mycobacterial infections: Acute kidney injury with hemoglobin casts. Case Reports in Nephrology, 2018, 9321621. https://doi.org/10.1155/2018/9321621
Mosaei, H., & Zenkin, N. (2020). Inhibition of RNA polymerase by rifampicin and rifamycin-like molecules. EcoSal Plus, 9(1). https://doi.org/10.1128/ecosalplus.esp-0017-2019
Lee, E. H., Baek, S. Y., Park, J. Y., & Kim, Y. W. (2020). Rifampicin activates AMPK and alleviates oxidative stress in the liver as mediated with Nrf2 signaling. Chemico-Biological Interactions, 315, 108889. https://doi.org/10.1016/j.cbi.2019.108889
Chen, B., Cao, H., Chen, L., Yang, X., Tian, X., Li, R., & Cheng, O. (2016). Rifampicin attenuated global cerebral ischemia injury via activating the nuclear factor erythroid 2-related factor pathway. Frontiers in Cellular Neuroscience, 10, 273. https://doi.org/10.3389/fncel.2016.00273
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007). Cell survival responses to environmental stresses via the keap1-Nrf2-ARE pathway. Annual Review of Pharmacology and Toxicology, 47(1), 89–116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046
Ma, Q. (2013). Role of Nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology, 53(1), 401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320
Bi, W., Cheng, X., Zeng, Z., Zhou, R., Luo, R., Zhang, J., & Zhu, L. (2021). Rifampicin ameliorates lipopolysaccharide-induced cognitive and motor impairments via inhibition of the TLR4/MyD88/NF-κB signaling pathway in mice. Neurological Research, 43(5), 358–371. https://doi.org/10.1080/01616412.2020.1866353
Pavek, P. (2016). Pregnane X receptor (PXR)-mediated gene repression and cross-talk of PXR with other nuclear receptors via coactivator interactions. Frontiers in Pharmacology, 7, 456. https://doi.org/10.3389/fphar.2016.00456
Saini, S. P. S., Mu, Y., Gong, H., Toma, D., Uppal, H., Ren, S., Li, S., Poloyac, S. M., & Xie, W. (2005). Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice†. Hepatology, 41(3), 497–505. https://doi.org/10.1002/hep.20570
Bhalla, S., Ozalp, C., Fang, S., Xiang, L., & Kemper, J. K. (2004). Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1α. Journal of Biological Chemistry, 279(43), 45139–45147. https://doi.org/10.1074/jbc.M405423200
Hyrsova, L., Smutny, T., Carazo, A., Moravcik, S., Mandikova, J., Trejtnar, F., Gerbal‐Chaloin, S., & Pavek, P. (2016). The pregnane X receptor down‐regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for (“squelching”) SRC‐1 coactivator. British Journal of Pharmacology, 173(10), 1703–1715. https://doi.org/10.1111/bph.13472
Li, T., & Chiang, J. Y. L. (2005). Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7α-hydroxylase gene transcription. American Journal of Physiology-Gastrointestinal and Liver Physiology, 288(1), G74–G84. https://doi.org/10.1152/ajpgi.00258.2004
Kodama, S., Moore, R., Yamamoto, Y., & Negishi, M. (2007). Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene. Biochemical Journal, 407(3), 373–381. https://doi.org/10.1042/BJ20070481
Gotoh, S., & Negishi, M. (2015). Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis. Scientific Reports, 5(1), 14076. https://doi.org/10.1038/srep14076
Bi, W., Zhu, L., Wang, C., Liang, Y., Liu, J., Shi, Q., & Tao, E. (2011). Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation. Brain Research, 1395, 12–20. https://doi.org/10.1016/j.brainres.2011.04.019
Gu, R.-Z., Tursun, A., Zhong, S.-J., Cheng, J.-B., Qin, X.-Y., & Cao, C. (2025). Protective effects of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside against cadmium toxicity involve BDNF/TrkB and PI3K/Akt signaling pathways. Biomedicine & Pharmacotherapy, 192, 118602. https://doi.org/10.1016/j.biopha.2025.118602
Liang, Y., Zhou, T., Chen, Y., Lin, D., Jing, X., Peng, S., Zheng, D., Zeng, Z., Lei, M., Wu, X., Huang, K., Yang, L., Xiao, S., Liu, J., & Tao, E. (2017). Rifampicin inhibits rotenone-induced microglial inflammation via enhancement of autophagy. NeuroToxicology, 63, 137–145. https://doi.org/10.1016/j.neuro.2017.09.015
Liang, Y., Zheng, D., Peng, S., Lin, D., Jing, X., Zeng, Z., Chen, Y., Huang, K., Xie, Y., Zhou, T., & Tao, E. (2020). Rifampicin attenuates rotenone-treated microglia inflammation via improving lysosomal function. Toxicology in Vitro, 63, 104690. https://doi.org/10.1016/j.tiv.2019.104690
Zhu, L., Yuan, Q., Zeng, Z., Zhou, R., Luo, R., Zhang, J., Tsang, C. K., & Bi, W. (2021). Rifampicin suppresses amyloid-β accumulation through enhancing autophagy in the hippocampus of a lipopolysaccharide-induced mouse model of cognitive decline. Journal of Alzheimer’s Disease, 79(3), 1171–1184. https://doi.org/10.3233/JAD-200690
Zhang, X., Zhang, H., Dong, J., Cai, H., & Le, W. (2025). Advances in autophagy for Parkinson’s disease pathogenesis and treatment. Ageing and Neurodegenerative Diseases, 5(1), 6. https://doi.org/10.20517/and.2024.33
Ferdous, J., Naitou, K., & Shiraishi, M. (2024). Distinct in vitro differentiation protocols differentially affect cytotoxicity induced by heavy metals in human neuroblastoma SH-SY5Y cells. Biological Trace Element Research, 203(5), 2595–2605. https://doi.org/10.1007/s12011-024-04342-x
Li, N., Cui, N., Li, T., Zhao, P., Bakry, I. A., Li, Q., Cheng, Y., Galaverna, G., Yang, H., & Wang, F. (2025). Pea peptides and heavy metal neurotoxicity: Exploring mechanisms and mitigation strategies in PC12 cells. Plant Foods for Human Nutrition, 80(1), 85. https://doi.org/10.1007/s11130-025-01322-x
Peng, J.-C., Deng, Y., Song, H.-X., Fang, Y.-Y., Gan, C.-L., Lin, J.-J., Luo, J.-J., Zheng, X.-W., Aschner, M., & Jiang, Y.-M. (2023). Protective effects of sodium para-aminosalicylic acid on lead and cadmium Co-exposure in SH-SY5Y cells. Brain Sciences, 13(3), 382. https://doi.org/10.3390/brainsci13030382
Mallamaci, R., Barbarossa, A., Carocci, A., & Meleleo, D. (2024). Evaluation of the potential protective effect of ellagic acid against heavy hetal (cadmium, hercury, and lead) toxicity in SH-SY5Y neuroblastoma cells. Foods, 13(3), 419. https://doi.org/10.3390/foods13030419
Jamsranjav, A., Gil, J., Kim, D., Choi, S., Park, H., Shin, Y., & Bae, O.-N. (2025). Quantitative neurotoxic effects of heavy metals and glutamate in mouse hippocampal neuronal cells. Environmental Analysis Health and Toxicology, 40(Special Issue), e2025s08. https://doi.org/10.5620/eaht.2025s08
Banaeeyeh, S., Razavi, B. M., & Hosseinzadeh, H. (2024). Neuroprotective effects of morin against cadmium- and arsenic-induced cell damage in PC12 neurons. Biological Trace Element Research, 203(6), 3272–3286. https://doi.org/10.1007/s12011-024-04407-x
Lior, N., Chen, D., Dan, F., & Ronit, P.-K. (2025). The connection between autophagy and Alzheimer’s disease. Inflammation Research, 74(1), 148. https://doi.org/10.1007/s00011-025-02118-0
Leite, M. N., de Paula, N. A., Ramalho, L. N. Z., & Frade, M. A. C. (2025). In vitro and ex vivo evaluation of rifampicin cytotoxicity in human skin models. Antibiotics, 14(7), 691. https://doi.org/10.3390/antibiotics14070691
Karri, V., Kumar, V., Ramos, D., Oliveira, E., & Schuhmacher, M. (2018). An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line. Toxicology Letters, 282, 25–36. https://doi.org/10.1016/j.toxlet.2017.10.002
Al-Ghafari, A., Elmorsy, E., Fikry, E., Alrowaili, M., & Carter, W. G. (2019). The heavy metals lead and cadmium are cytotoxic to human bone osteoblasts via induction of redox stress. PLOS ONE, 14(11), e0225341. https://doi.org/10.1371/journal.pone.0225341
Xicoy, H., Wieringa, B., & Martens, G. J. M. (2017). The SH-SY5Y cell line in Parkinson’s disease research: A systematic review. Molecular Neurodegeneration, 12(1), 10. https://doi.org/10.1186/s13024-017-0149-0
Murphy, M. P., Bayir, H., Belousov, V., Chang, C. J., Davies, K. J. A., Davies, M. J., Dick, T. P., Finkel, T., Forman, H. J., Janssen-Heininger, Y., Gems, D., Kagan, V. E., Kalyanaraman, B., Larsson, N.-G., Milne, G. L., Nyström, T., Poulsen, H. E., Radi, R., Van Remmen, H., … Halliwell, B. (2022). Guidelines for measuring reactive oxygen species and oxidative damage in cells and in vivo. Nature Metabolism, 4(6), 651–662. https://doi.org/10.1038/s42255-022-00591-z
Wang, S., Ren, X., Hu, X., Zhou, L., Zhang, C., & Zhang, M. (2019). Cadmium-induced apoptosis through reactive oxygen species-mediated mitochondrial oxidative stress and the JNK signaling pathway in TM3 cells, a model of mouse Leydig cells. Toxicology and Applied Pharmacology, 368, 37–48. https://doi.org/10.1016/j.taap.2019.02.012
Wu, J. L., Wang, H. Y., Cheng, Y. L., Du, C., & Qian, H. (2015). Neuroprotective effects of torularhodin against H2O2-induced oxidative injury and apoptosis in PC12 cells. Pharmazie, 70(1), 17–23. https://doi.org/10.1691/PH.2015.4699

Ayrıntılar

Birincil Dil

İngilizce

Konular

Hücre Nörokimyası, Biyokimya ve Hücre Biyolojisi (Diğer)

Bölüm

Derleme

Yazarlar

Dilek Karataş ^*
0000-0003-1505-1997
Türkiye

Tugce Karaduman Yesıldal
0000-0003-0728-0968
Türkiye

Erken Görünüm Tarihi

22 Nisan 2026

Yayımlanma Tarihi

-

Gönderilme Tarihi

4 Şubat 2026

Kabul Tarihi

3 Nisan 2026

Yayımlandığı Sayı

Yıl 2026 Sayı: Advanced Online Publication

DOI

https://doi.org/10.29002/asujse.1881741

IZ

https://izlik.org/JA84PG33RK

Kaynak Göster

RIS / Bibtex

APA

Karataş, D., & Karaduman Yesıldal, T. (2026). Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings. Aksaray University Journal of Science and Engineering, Advanced Online Publication, 11-31. https://doi.org/10.29002/asujse.1881741

AMA

1.Karataş D, Karaduman Yesıldal T. Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings. Aksaray J. Sci. Eng. 2026;(Advanced Online Publication):11-31. doi:10.29002/asujse.1881741

Chicago

Karataş, Dilek, ve Tugce Karaduman Yesıldal. 2026. “Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings”. Aksaray University Journal of Science and Engineering, sy Advanced Online Publication: 11-31. https://doi.org/10.29002/asujse.1881741.

EndNote

Karataş D, Karaduman Yesıldal T (01 Nisan 2026) Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings. Aksaray University Journal of Science and Engineering Advanced Online Publication 11–31.

IEEE

[1]D. Karataş ve T. Karaduman Yesıldal, “Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings”, Aksaray J. Sci. Eng., sy Advanced Online Publication, ss. 11–31, Nis. 2026, doi: 10.29002/asujse.1881741.

ISNAD

Karataş, Dilek - Karaduman Yesıldal, Tugce. “Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings”. Aksaray University Journal of Science and Engineering. Advanced Online Publication (01 Nisan 2026): 11-31. https://doi.org/10.29002/asujse.1881741.

JAMA

1.Karataş D, Karaduman Yesıldal T. Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings. Aksaray J. Sci. Eng. 2026;:11–31.

MLA

Karataş, Dilek, ve Tugce Karaduman Yesıldal. “Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings”. Aksaray University Journal of Science and Engineering, sy Advanced Online Publication, Nisan 2026, ss. 11-31, doi:10.29002/asujse.1881741.

Vancouver

1.Dilek Karataş, Tugce Karaduman Yesıldal. Molecular Foundations of Heavy Metal-Induced Neurotoxicity and the Neuroprotective Role of Rifampicin: A Review of Current Findings. Aksaray J. Sci. Eng. 01 Nisan 2026;(Advanced Online Publication):11-3. doi:10.29002/asujse.1881741