Molecular mechanisms of programmed cell death and potential targeted pharmacotherapy in ischemic stroke (Review)
- Authors:
- Wan-Li Duan
- Li-Hui Gu
- Ai Guo
- Xue-Jie Wang
- Yi-Yue Ding
- Peng Zhang
- Bao-Gang Zhang
- Qin Li
- Li-Xia Yang
-
Affiliations: Medical Research Center, Shaoxing People's Hospital, Shaoxing, Zhejiang 312000, P.R. China, Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261041, P.R. China, Department of Diagnostic Pathology, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261041, P.R. China, Department of Cardiology, Shaoxing People's Hospital, Shaoxing, Zhejiang 312000, P.R. China, Rehabilitation Medicine and Health College, Hunan University of Medicine, Huaihua, Hunan 418000, P.R. China, Medical Research Center, Shaoxing People's Hospital, Shaoxing, Zhejiang 312000, P.R. China - Published online on: May 6, 2025 https://doi.org/10.3892/ijmm.2025.5544
- Article Number: 103
-
Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
 |
 |
 |
 |
 |
|
Katan M and Luft A: Global burden of stroke. Semin Neurol. 38:208–211. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, et al: Heart disease and stroke statistics-2018 update: A report from the American heart association. Circulation. 137:e67–e492. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Tao T, Liu M, Chen M, Wang C, Xu T, Jiang Y, Guo Y and Zhang JH: Natural medicine in neuroprotection for ischemic stroke: Challenges and prospective. Pharmacol Ther. 216:1076952020. View Article : Google Scholar : PubMed/NCBI | |
|
Datta A, Sarmah D, Mounica L, Kaur H, Kesharwani R, Verma G, Veeresh P, Kotian V, Kalia K, Borah A, et al: Cell death pathways in ischemic stroke and targeted pharmacotherapy. Transl Stroke Res. 11:1185–1202. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Guo J, Tuo QZ and Lei P: Iron, ferroptosis, and ischemic stroke. J Neurochem. 165:487–520. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Adibhatla RM and Hatcher JF: Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies. CNS Neurol Disord Drug Targets. 7:243–253. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Mosconi MG and Paciaroni M: Treatments in ischemic stroke: Current and future. Eur Neurol. 85:349–366. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chai Z, Zheng J and Shen J: Mechanism of ferroptosis regulating ischemic stroke and pharmacologically inhibiting ferroptosis in treatment of ischemic stroke. CNS Neurosci Ther. 30:e148652024. View Article : Google Scholar : PubMed/NCBI | |
|
Hou Z and Brenner JS: Developing targeted antioxidant nanomedicines for ischemic penumbra: Novel strategies in treating brain ischemia-reperfusion injury. Redox Biol. 73:1031852024. View Article : Google Scholar : PubMed/NCBI | |
|
Lockshin RA and Williams CM: programmed cell death-I. Cytology of degeneration in the intersegmental muscles of the pernyi silkmoth. J Insect Physiol. 11:123–133. 1965. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao Y, Zhang X, Chen X and Wei Y: Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review). Int J Mol Med. 49:152022. View Article : Google Scholar : | |
|
Qin C, Yang S, Chu YH, Zhang H, Pang XW, Chen L, Zhou LQ, Chen M, Tian DS and Wang W: Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 7:2152022. View Article : Google Scholar : PubMed/NCBI | |
|
Gong Z, Guo J, Liu B, Guo Y, Cheng C, Jiang Y, Liang N, Hu M, Song T, Yang L, et al: Mechanisms of immune response and cell death in ischemic stroke and their regulation by natural compounds. Front Immunol. 14:12878572024. View Article : Google Scholar : PubMed/NCBI | |
|
Long J, Sun Y, Liu S, Yang S, Chen C, Zhang Z, Chu S, Yang Y, Pei G, Lin M, et al: Targeting pyroptosis as a preventive and therapeutic approach for stroke. Cell Death Discov. 9:1552023. View Article : Google Scholar : PubMed/NCBI | |
|
Newton K, Strasser A, Kayagaki N and Dixit VM: Cell death. Cell. 187:235–256. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Kerr JF, Wyllie AH and Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 26:239–257. 1972. View Article : Google Scholar : PubMed/NCBI | |
|
Broughton BR, Reutens DC and Sobey CG: Apoptotic mechanisms after cerebral ischemia. Stroke. 40:e331–e339. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Nano M and Montell DJ: Apoptotic signaling: Beyond cell death. Semin Cell Dev Biol. 156:22–34. 2024. View Article : Google Scholar | |
|
Mizushima N and Komatsu M: Autophagy: Renovation of cells and tissues. Cell. 147:728–741. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zhao S, Li X, Wang J and Wang H: The role of the effects of autophagy on NLRP3 inflammasome in inflammatory nervous system diseases. Front Cell Dev Biol. 9:6574782021. View Article : Google Scholar : PubMed/NCBI | |
|
Edinger AL and Thompson CB: Death by design: Apoptosis, necrosis and autophagy. Curr Opin Cell Biol. 16:663–669. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
de Almagro MC and Vucic D: Necroptosis: Pathway diversity and characteristics. Semin Cell Dev Biol. 39:56–62. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Festjens N, Vanden Berghe T and Vandenabeele P: Necrosis, a well-orchestrated form of cell demise: Signalling cascades, important mediators and concomitant immune response. Biochim Biophys Acta. 1757:1371–1387. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Chaudhary GR, Yadav PK, Yadav AK, Tiwari M, Gupta A, Sharma A, Sahu K, Pandey AN, Pandey AK and Chaube SK: Necrosis and necroptosis in germ cell depletion from mammalian ovary. J Cell Physiol. 234:8019–8027. 2019. View Article : Google Scholar | |
|
Zychlinsky A, Prevost MC and Sansonetti PJ: Shigella flexneri induces apoptosis in infected macrophages. Nature. 358:167–169. 1992. View Article : Google Scholar : PubMed/NCBI | |
|
Yu P, Zhang X, Liu N, Tang L, Peng C and Chen X: Pyroptosis: Mechanisms and diseases. Signal Transduct Target Ther. 6:1282021. View Article : Google Scholar : PubMed/NCBI | |
|
Bertheloot D, Latz E and Franklin BS: Necroptosis, pyroptosis and apoptosis: An intricate game of cell death. Cell Mol Immunol. 18:1106–1121. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang X, Stockwell BR and Conrad M: Ferroptosis: Mechanisms, biology and role in disease. Nat Rev Mol Cell Biol. 22:266–282. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Dixon SJ and Olzmann JA: The cell biology of ferroptosis. Nat Rev Mol Cell Biol. 25:424–442. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Li J, Xu P, Hong Y, Xie Y, Peng M, Sun R, Guo H, Zhang X, Zhu W, Wang J and Liu X: Lipocalin-2-mediated astrocyte pyroptosis promotes neuroinflammatory injury via NLRP3 inflammasome activation in cerebral ischemia/reperfusion injury. J Neuroinflammation. 20:1482023. View Article : Google Scholar : PubMed/NCBI | |
|
Cai D, Fraunfelder M, Fujise K and Chen SY: ADAR1 exacerbates ischemic brain injury via astrocyte-mediated neuron apoptosis. Redox Biol. 67:1029032023. View Article : Google Scholar : PubMed/NCBI | |
|
Culmsee C and Mattson MP: p53 in neuronal apoptosis. Biochem Biophys Res Commun. 331:761–777. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Radak D, Katsiki N, Resanovic I, Jovanovic A, Sudar-Milovanovic E, Zafirovic S, Mousad SA and Isenovic ER: Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 15:115–122. 2017. View Article : Google Scholar | |
|
Cregan SP, Arbour NA, Maclaurin JG, Callaghan SM, Fortin A, Cheung EC, Guberman DS, Park DS and Slack RS: p53 activation domain 1 is essential for PUMA upregulation and p53-mediated neuronal cell death. J Neurosci. 24:10003–10012. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Nakka VP, Gusain A, Mehta SL and Raghubir R: Molecular mechanisms of apoptosis in cerebral ischemia: Multiple neuroprotective opportunities. Mol Neurobiol. 37:7–38. 2008. View Article : Google Scholar | |
|
Ashkenazi A: Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2:420–430. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Love S: Apoptosis and brain ischaemia. Prog Neuropsychopharmacol Biol Psychiatry. 27:267–282. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Velier JJ, Ellison JA, Kikly KK, Spera PA, Barone FC and Feuerstein GZ: Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat. J Neurosci. 19:5932–5941. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Rupalla K, Allegrini PR, Sauer D and Wiessner C: Time course of microglia activation and apoptosis in various brain regions after permanent focal cerebral ischemia in mice. Acta Neuropathol. 96:172–178. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Botchkina GI, Geimonen E, Bilof ML, Villarreal O and Tracey KJ: Loss of NF-kappaB activity during cerebral ischemia and TNF cytotoxicity. Mol Med. 5:372–381. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Sarmah D, Kaur H, Saraf J, Vats K, Pravalika K, Wanve M, Kalia K, Borah A, Kumar A, Wang X, et al: Mitochondrial dysfunction in stroke: implications of stem cell therapy. Transl Stroke Res. 2018.Epub ahead of print. PubMed/NCBI | |
|
Edlich F: BCL-2 proteins and apoptosis: Recent insights and unknowns. Biochem Biophys Res Commun. 500:26–34. 2018. View Article : Google Scholar | |
|
Harada H and Grant S: Apoptosis regulators. Rev Clin Exp Hematol. 7:117–138. 2003. | |
|
Yin XM: Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res. 10:161–167. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Sugawara T, Fujimura M, Noshita N, Kim GW, Saito A, Hayashi T, Narasimhan P, Maier CM and Chan PH: Neuronal death/survival signaling pathways in cerebral ischemia. NeuroRx. 1:17–25. 2004. View Article : Google Scholar | |
|
Polster BM and Fiskum G: Mitochondrial mechanisms of neural cell apoptosis. J Neurochem. 90:1281–1289. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Zhai D, Chin K, Wang M and Liu F: Disruption of the nuclear p53-GAPDH complex protects against ischemia-induced neuronal damage. Mol Brain. 7:202014. View Article : Google Scholar : PubMed/NCBI | |
|
Gao J, Liu J, Li Y, Liu J, Wang H, Chai M, Dong Y, Zhang Z, Su G and Wang M: Targeting p53 for neuroinflammation: New therapeutic strategies in ischemic stroke. J Neurosci Res. 101:1393–1408. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Morrison RS, Kinoshita Y, Johnson MD, Guo W and Garden GA: p53-dependent cell death signaling in neurons. Neurochem Res. 28:15–27. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Mattson MP: Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 1:120–129. 2000. View Article : Google Scholar | |
|
Nakano K and Vousden KH: PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell. 7:683–694. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Wu D and Wang H: Hydrogen sulfide plays an important protective role by influencing autophagy in diseases. Physiol Res. 68:335–345. 2019.PubMed/NCBI | |
|
He C and Klionsky DJ: Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 43:67–93. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Guan R, Zou W, Dai X, Yu X, Liu H, Chen Q and Teng W: Mitophagy, a potential therapeutic target for stroke. J Biomed Sci. 25:872018. View Article : Google Scholar : PubMed/NCBI | |
|
Scrivo A, Bourdenx M, Pampliega O and Cuervo AM: Selective autophagy as a potential therapeutic target for neurodegenerative disorders. Lancet Neurol. 17:802–815. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wang X, Fang Y, Huang Q, Xu P, Lenahan C, Lu J, Zheng J, Dong X, Shao A and Zhang J: An updated review of autophagy in ischemic stroke: From mechanisms to therapies. Exp Neurol. 340:1136842021. View Article : Google Scholar : PubMed/NCBI | |
|
Solenski NJ, diPierro CG, Trimmer PA, Kwan AL and Helm GA: Ultrastructural changes of neuronal mitochondria after transient and permanent cerebral ischemia. Stroke. 33:816–824. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Jung CH, Ro SH, Cao J, Otto NM and Kim DH: mTOR regulation of autophagy. FEBS Lett. 584:1287–1295. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Kim YC and Guan KL: mTOR: A pharmacologic target for autophagy regulation. J Clin Invest. 125:25–32. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Wang B, Liu Y, Guo Y, Lu H and Liu X: Inhibition of PI3K/Akt/mTOR signaling by NDRG2 contributes to neuronal apoptosis and autophagy in ischemic stroke. J Stroke Cerebrovasc Dis. 32:1069842023. View Article : Google Scholar : PubMed/NCBI | |
|
Cui DR, Wang L, Jiang W, Qi AH, Zhou QH and Zhang XL: Propofol prevents cerebral ischemia-triggered autophagy activation and cell death in the rat hippocampus through the NF-κB/p53 signaling pathway. Neuroscience. 246:117–132. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Bootman MD, Chehab T, Bultynck G, Parys JB and Rietdorf K: The regulation of autophagy by calcium signals: Do we have a consensus? Cell Calcium. 70:32–46. 2018. View Article : Google Scholar | |
|
Li L, Li L, Zhou X, Yu Y, Li Z, Zuo D and Wu Y: Silver nanoparticles induce protective autophagy via Ca(2+)/CaMKKβ/AMPK/mTOR pathway in SH-SY5Y cells and rat brains. Nanotoxicology. 13:369–391. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Shi W, Xu D, Gu J, Xue C, Yang B, Fu L, Song S, Liu D, Zhou W, Lv J, et al: Saikosaponin-d inhibits proliferation by up-regulating autophagy via the CaMKKβ-AMPK-mTOR pathway in ADPKD cells. Mol Cell Biochem. 449:219–226. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Krishna M and Narang H: The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci. 65:3525–3544. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Li H, Zhou S, Wu L, Liu K, Zhang Y, Ma G and Wang L: The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury. J Neurol Sci. 357:270–275. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Song YQ, Zou HL, Zhao YJ, Yu LQ, Tan ZX and Kong R: Activation of p38-mitogen-activated protein kinase contributes to ischemia reperfusion in rat brain. Genet Mol Res. 15:gmr.150384922016. View Article : Google Scholar | |
|
Ferrer I, Friguls B, Dalfó E and Planas AM: Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol. 105:425–437. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Oberstein A, Jeffrey PD and Shi Y: Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein. J Biol Chem. 282:13123–13132. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Xu F, Gu JH and Qin ZH: Neuronal autophagy in cerebral ischemia. Neurosci Bull. 28:658–666. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Chen W, Sun Y, Liu K and Sun X: Autophagy: A double-edged sword for neuronal survival after cerebral ischemia. Neural Regen Res. 9:1210–1216. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Marquez RT and Xu L: Bcl-2:Beclin 1 complex: Multiple, mechanisms regulating autophagy/apoptosis toggle switch. Am J Cancer Res. 2:214–221. 2012.PubMed/NCBI | |
|
Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD and Levine B: Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell. 122:927–939. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Ham PB III and Raju R: Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol. 157:92–116. 2017. View Article : Google Scholar | |
|
Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM and Chung J: Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 441:1157–1161. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Liu K, Sun Y, Gu Z, Shi N, Zhang T and Sun X: Mitophagy in ischaemia/reperfusion induced cerebral injury. Neurochem Res. 38:1295–1300. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Choe SC, Hamacher-Brady A and Brady NR: Autophagy capacity and sub-mitochondrial heterogeneity shape Bnip3-induced mitophagy regulation of apoptosis. Cell Commun Signal. 13:372015. View Article : Google Scholar : PubMed/NCBI | |
|
Jang W and Haucke V: ER remodeling via lipid metabolism. Trends Cell Biol. 34:942–954. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Gubas A and Dikic I: ER remodeling via ER-phagy. Mol Cell. 82:1492–1500. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Garcia-Huerta P, Troncoso-Escudero P, Jerez C, Hetz C and Vidal RL: The intersection between growth factors autophagy and ER stress: A new target to treat neurodegenerative diseases? Brain Res. 1649(Pt B): 173–180. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Yin Y, Sun G, Li E, Kiselyov K and Sun D: ER stress and impaired autophagy flux in neuronal degeneration and brain injury. Ageing Res Rev. 34:3–14. 2017. View Article : Google Scholar : | |
|
Jun-Long H, Yi L, Bao-Lian Z, Jia-Si L, Ning Z, Zhou-Heng Y, Xue-Jun S and Wen-Wu L: Necroptosis signaling pathways in stroke: From mechanisms to therapies. Curr Neuropharmacol. 16:1327–1339. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B and Tschopp J: Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 1:489–495. 2000. View Article : Google Scholar | |
|
Moriwaki K and Chan FK: RIP3: A molecular switch for necrosis and inflammation. Genes Dev. 27:1640–1649. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Vieira M, Fernandes J, Carreto L, Anuncibay-Soto B, Santos M, Han J, Fernández-López A, Duarte CB, Carvalho AL and Santos AE: Ischemic insults induce necroptotic cell death in hippocampal neurons through the up-regulation of endogenous RIP3. Neurobiol Dis. 68:26–36. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X and Wang X: Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 148:213–227. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H and Vandenabeele P: Regulated necrosis: The expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 15:135–147. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Weber K, Roelandt R, Bruggeman I, Estornes Y and Vandenabeele P: Nuclear RIPK3 and MLKL contribute to cytosolic necrosome formation and necroptosis. Commun Biol. 1:62018. View Article : Google Scholar : PubMed/NCBI | |
|
Feng Y, Li M, Yangzhong X, Zhang X, Zu A, Hou Y, Li L and Sun S: Pyroptosis in inflammation-related respiratory disease. J Physiol Biochem. 78:721–737. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Xia S, Hollingsworth LR IV and Wu H: Mechanism and regulation of gasdermin-mediated cell death. Cold Spring Harb Perspect Biol. 12:a0364002020. View Article : Google Scholar | |
|
Liu X, Xia S, Zhang Z, Wu H and Lieberman J: Channelling inflammation: Gasdermins in physiology and disease. Nat Rev Drug Discov. 20:384–405. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H and Lieberman J: Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 535:153–158. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Wang K, Sun Q, Zhong X, Zeng M, Zeng H, Shi X, Li Z, Wang Y, Zhao Q, Shao F and Ding J: Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell. 180:941–955.e20. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Fritsch M, Günther SD, Schwarzer R, Albert MC, Schorn F, Werthenbach JP, Schiffmann LM, Stair N, Stocks H, Seeger JM, et al: Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature. 575:683–687. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, Junqueira C, Meza-Sosa KF, Mok TMY, Ansara J, et al: Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature. 579:415–420. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, et al: Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 526:666–671. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Dong Z, Pan K, Pan J, Peng Q and Wang Y: The possibility and molecular mechanisms of cell pyroptosis after cerebral ischemia. Neurosci Bull. 34:1131–1136. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kono H, Kimura Y and Latz E: Inflammasome activation in response to dead cells and their metabolites. Curr Opin Immunol. 30:91–98. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Huang Y, Xu W and Zhou R: NLRP3 inflammasome activation and cell death. Cell Mol Immunol. 18:2114–2127. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Puleo MG, Miceli S, Di Chiara T, Pizzo GM, Della Corte V, Simonetta I, Pinto A and Tuttolomondo A: Molecular mechanisms of inflammasome in ischemic stroke pathogenesis. Pharmaceuticals (Basel). 15:11682022. View Article : Google Scholar : PubMed/NCBI | |
|
Fu R, Zhao L, Guo Y, Qin X, Xu W, Cheng X, Zhang Y and Xu S: AIM2 inflammasome: A potential therapeutic target in ischemic stroke. Clin Immunol. 259:1098812024. View Article : Google Scholar | |
|
Mitchell PS, Sandstrom A and Vance RE: The NLRP1 inflammasome: New mechanistic insights and unresolved mysteries. Curr Opin Immunol. 60:37–45. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Duan WL, Wang XJ, Ma YP, Sheng ZM, Dong H, Zhang LY, Zhang BG and He MT: Therapeutic strategies targeting the NLRP3-mediated inflammatory response and pyroptosis in cerebral ischemia/reperfusion injury (Review). Mol Med Rep. 29:462024. View Article : Google Scholar | |
|
Duncan JA and Canna SW: The NLRC4 inflammasome. Immunol Rev. 281:115–123. 2018. View Article : Google Scholar : | |
|
Man SM and Kanneganti TD: Regulation of inflammasome activation. Immunol Rev. 265:6–21. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Hu X, Bao Y, Li M, Zhang W and Chen C: The role of ferroptosis and its mechanism in ischemic stroke. Exp Neurol. 372:1146302024. View Article : Google Scholar | |
|
Lei G, Zhuang L and Gan B: Targeting ferroptosis as a vulnerability in cancer. Nat Rev Cancer. 22:381–396. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Chen J, Yang L, Geng L, He J, Chen L, Sun Q, Zhao J and Wang X: Inhibition of Acyl-CoA Synthetase long-chain family member 4 facilitates neurological recovery after stroke by regulation ferroptosis. Front Cell Neurosci. 15:6323542021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang L, Bai XY, Sun KY, Li X, Zhang ZQ, Liu YD, Xiang Y and Liu XL: A new perspective in the treatment of ischemic stroke: Ferroptosis. Neurochem Res. 49:815–833. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Ma N, Xu J, Zhang Y, Yang P, Su X, Xing Y, An N, Yang F, Zhang G, et al: Targeting ferroptosis: Pathological mechanism and treatment of ischemia-reperfusion injury. Oxid Med Cell Longev. 2021:15879222021. View Article : Google Scholar : PubMed/NCBI | |
|
Das UN: Saturated fatty acids, MUFAs and PUFAs regulate ferroptosis. Cell Chem Biol. 26:309–311. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Bu ZQ, Yu HY, Wang J, He X, Cui YR, Feng JC and Feng J: Emerging role of ferroptosis in the pathogenesis of ischemic stroke: A new therapeutic target? ASN Neuro. 13:175909142110375052021. View Article : Google Scholar : PubMed/NCBI | |
|
Zou Y, Li H, Graham ET, Deik AA, Eaton JK, Wang W, Sandoval-Gomez G, Clish CB, Doench JG and Schreiber SL: Cytochrome P450 oxidoreductase contributes to phospholipid peroxidation in ferroptosis. Nat Chem Biol. 16:302–309. 2020. View Article : Google Scholar : PubMed/NCBI | |
|
Muralikrishna Adibhatla R and Hatcher JF: Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med. 40:376–387. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Liu X: Changes and significance of serum CXCL-16, GDF-15, PLA-2 levels in patients with cerebral infarction. Am J Transl Res. 13:5617–5622. 2021.PubMed/NCBI | |
|
Tuo QZ, Liu Y, Xiang Z, Yan HF, Zou T, Shu Y, Ding XL, Zou JJ, Xu S, Tang F, et al: Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion. Signal Transduct Target Ther. 7:592022. View Article : Google Scholar : PubMed/NCBI | |
|
Cheng G, Zhao W, Xin Y, Huang G and Liu Y, Li Z, Zhan M, Li Y, Lu L, van Leyen K and Liu Y: Effects of ML351 and tissue plasminogen activator combination therapy in a rat model of focal embolic stroke. J Neurochem. 157:586–598. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Yigitkanli K, Zheng Y, Pekcec A, Lo EH and van Leyen K: Increased 12/15-lipoxygenase leads to widespread brain injury following global cerebral ischemia. Transl Stroke Res. 8:194–202. 2017. View Article : Google Scholar : | |
|
Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE and Fleming MD: Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Nat Genet. 37:1264–1269. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Ji C and Kosman DJ: Molecular mechanisms of nontransferrin-bound and transferring-bound iron uptake in primary hippocampal neurons. J Neurochem. 133:668–683. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Philpott CC, Patel SJ and Protchenko O: Management versus miscues in the cytosolic labile iron pool: The varied functions of iron chaperones. Biochim Biophys Acta Mol Cell Res. 1867:1188302020. View Article : Google Scholar : PubMed/NCBI | |
|
Dietrich RB and Bradley WG Jr: Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children. Radiology. 168:203–206. 1988. View Article : Google Scholar : PubMed/NCBI | |
|
Kondo Y, Ogawa N, Asanuma M, Ota Z and Mori A: Regional differences in late-onset iron deposition, ferritin, transferrin, astrocyte proliferation, and microglial activation after transient forebrain ischemia in rat brain. J Cereb Blood Flow Metab. 15:216–226. 1955. View Article : Google Scholar | |
|
DeGregorio-Rocasolano N, Martí-Sistac O, Ponce J, Castelló-Ruiz M, Millán M, Guirao V, García-Yébenes I, Salom JB, Ramos-Cabrer P, Alborch E, et al: Iron-loaded transferrin (Tf) is detrimental whereas iron-free Tf confers protection against brain ischemia by modifying blood Tf saturation and subsequent neuronal damage. Redox Biol. 15:143–158. 2018. View Article : Google Scholar : | |
|
Ingrassia R, Lanzillotta A, Sarnico I, Benarese M, Blasi F, Borgese L, Bilo F, Depero L, Chiarugi A, Spano PF and Pizzi M: 1B/(-)IRE DMT1 expression during brain ischemia contributes to cell death mediated by NF-κB/RelA acetylation at Lys310. PLoS One. 7:e380192012. View Article : Google Scholar | |
|
Hirayama Y and Koizumi S: Hypoxia-independent mechanisms of HIF-1α expression in astrocytes after ischemic preconditioning. Glia. 65:523–530. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Yang L, Wang D, Wang XT, Lu YP and Zhu L: The roles of hypoxia-inducible Factor-1 and iron regulatory protein 1 in iron uptake induced by acute hypoxia. Biochem Biophys Res Commun. 507:128–135. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Chen W, Jiang L, Hu Y, Tang N, Liang N, Li XF, Chen YW, Qin H and Wu L: Ferritin reduction is essential for cerebral ischemia-induced hippocampal neuronal death through p53/SLC7A11-mediated ferroptosis. Brain Res. 1752:1472162021. View Article : Google Scholar | |
|
Wu Q, Wu WS, Su L, Zheng X, Wu WY, Santambrogio P, Gou YJ, Hao Q, Wang PN, Li YR, et al: Mitochondrial ferritin is a hypoxia-inducible factor 1α-inducible gene that protects from hypoxia-induced cell death in brain. Antioxid Redox Signal. 30:198–212. 2019. View Article : Google Scholar | |
|
Wang P, Cui Y, Ren Q, Yan B, Zhao Y, Yu P, Gao G, Shi H, Chang S and Chang YZ: Mitochondrial ferritin attenuates cerebral ischaemia/reperfusion injury by inhibiting ferroptosis. Cell Death Dis. 12:4472021. View Article : Google Scholar : PubMed/NCBI | |
|
Sanguigno L, Guida N, Anzilotti S, Cuomo O, Mascolo L, Serani A, Brancaccio P, Pennacchio G, Licastro E, Pignataro G, et al: Stroke by inducing HDAC9-dependent deacetylation of HIF-1 and Sp1, promotes TfR1 transcription and GPX4 reduction, thus determining ferroptotic neuronal death. Int J Biol Sci. 19:2695–2710. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Li C, Sun G, Chen B, Xu L, Ye Y, He J, Bao Z, Zhao P, Miao Z, Zhao L, et al: Nuclear receptor coactivator 4-mediated ferritinophagy contributes to cerebral ischemia-induced ferroptosis in ischemic stroke. Pharmacol Res. 174:1059332021. View Article : Google Scholar : PubMed/NCBI | |
|
Słomka A, Świtońska M and Żekanowska E: Hepcidin levels are increased in patients with acute ischemic stroke: Preliminary report. J Stroke Cerebrovasc Dis. 24:1570–1576. 2015. View Article : Google Scholar | |
|
Ding H, Yan CZ, Shi H, Zhao YS, Chang SY, Yu P, Wu WS, Zhao CY, Chang YZ and Duan XL: Hepcidin is involved in iron regulation in the ischemic brain. PLoS One. 6:e253242011. View Article : Google Scholar : | |
|
Zhu K, Zhu X, Liu S, Yu J, Wu S and Hei M: Glycyrrhizin attenuates hypoxic-ischemic brain damage by inhibiting ferroptosis and neuroinflammation in neonatal rats via the HMGB1/GPX4 pathway. Oxid Med Cell Longev. 2022:84385282022. View Article : Google Scholar : | |
|
Shi Y, Han L, Zhang X, Xie L, Pan P and Chen F: Selenium alleviates cerebral ischemia/reperfusion injury by regulating oxidative stress, mitochondrial fusion and ferroptosis. Neurochem Res. 47:2992–3002. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Guan X, Li Z, Zhu S, Cheng M, Ju Y, Ren L, Yang G and Min D: Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils. Life Sci. 264:1186602021. View Article : Google Scholar | |
|
Zhang Y, Lu X, Tai B, Li W and Li T: Ferroptosis and its multifaceted roles in cerebral stroke. Front Cell Neurosci. 15:6153722021. View Article : Google Scholar : PubMed/NCBI | |
|
Fu C, Wu Y, Liu S, Luo C, Lu Y, Liu M, Wang L, Zhang Y and Liu X: Rehmannioside A improves cognitive impairment and alleviates ferroptosis via activating PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathway after ischemia. J Ethnopharmacol. 289:1150212022. View Article : Google Scholar : PubMed/NCBI | |
|
Haas S, Weidner N and Winkler J: Adult stem cell therapy in stroke. Curr Opin Neurol. 18:59–64. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Tuo QZ, Zhang ST and Lei P: Mechanisms of neuronal cell death in ischemic stroke and their therapeutic implications. Med Res Rev. 42:259–305. 2022. View Article : Google Scholar | |
|
Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Chen B, Wang G, Li W, Liu W, Lin R, Tao J, Jiang M, Chen L and Wang Y: Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke. Exp Cell Res. 351:163–172. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Zhang Y, Tang S, Yu L, Zhao Y, Ren Q, Huang X, Xu W, Huang M and Peng J: Pien-Tze-Huang protects cerebral ischemic injury by inhibiting neuronal apoptosis in acute ischemic stroke rats. J Ethnopharmacol. 219:117–125. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Nie Y, Wen L, Li H, Song J, Wang N, Huang L, Gao L and Qu M: Tanhuo formula inhibits astrocyte activation and apoptosis in acute ischemic stroke. Front Pharmacol. 13:8592442022. View Article : Google Scholar : PubMed/NCBI | |
|
Mei ZG, Tan LJ, Wang JF, Li XL, Huang WF and Zhou HJ: Fermented Chinese formula Shuan-Tong-Ling attenuates ischemic stroke by inhibiting inflammation and apoptosis. Neural Regen Res. 12:425–432. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Zhang W, Ma B, Zhang H, Fan Z, Li M and Li X: A novel biscoumarin derivative dephosphorylates ERK and alleviates apoptosis induced by mitochondrial oxidative damage in ischemic stroke mice. Life Sci. 264:1184992021. View Article : Google Scholar | |
|
Raghavan A and Shah ZA: Withania somnifera improves ischemic stroke outcomes by attenuating PARP1-AIF-mediated caspase-independent apoptosis. Mol Neurobiol. 52:1093–1105. 2015. View Article : Google Scholar | |
|
Peng T, Li S, Liu L, Yang C, Farhan M, Chen L, Su Q and Zheng W: Artemisinin attenuated ischemic stroke induced cell apoptosis through activation of ERK1/2/CREB/BCL-2 signaling pathway in vitro and in vivo. Int J Biol Sci. 18:4578–4594. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Hu S, Cao Q, Xu P, Ji W, Wang G and Zhang Y: Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats. Exp Ther Med. 11:1005–1010. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Liu T, Wang W, Li X, Chen Y, Mu F, Wen A, Liu M and Ding Y: Advances of phytotherapy in ischemic stroke targeting PI3K/Akt signaling. Phytother Res. 37:5509–5528. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Hafeez A, Elmadhoun O, Peng C, Ding JY, Geng X, Guthikonda M and Ding Y: Reduced apoptosis by ethanol and its association with PKC-δ and Akt signaling in ischemic stroke. Aging Dis. 5:366–372. 2014.PubMed/NCBI | |
|
Fan W, Li X, Huang L, He S, Xie Z, Fu Y, Fang W and Li Y: S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K/Akt/GSK3β signal pathway in rats. Neurochem Int. 115:50–60. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Xu Y, Chen W, Chen Z, Huang M, Yang F and Zhang Y: Mechanism of action of xiaoyao san in treatment of ischemic stroke is related to anti-apoptosis and activation of PI3K/Akt pathway. Drug Des Devel Ther. 15:753–767. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang C, Chen H, Jiang HH, Mao BB and Yu H: Total flavonoids of chuju decrease oxidative stress and cell apoptosis in ischemic stroke rats: Network and experimental analyses. Front Neurosci. 15:7724012021. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang SS, Liu M, Liu DN, Shang YF, Du GH and Wang YH: Network pharmacology analysis and experimental validation of kaempferol in the treatment of ischemic stroke by inhibiting apoptosis and regulating neuroinflammation involving neutrophils. Int J Mol Sci. 23:126942022. View Article : Google Scholar : PubMed/NCBI | |
|
Luo Y, Cheng J, Fu Y, Zhang M, Gou M, Li J, Li X, Bai J, Zhou Y, Zhang L and Gao D: D-allose Inhibits TLR4/PI3K/AKT signaling to attenuate neuroinflammation and neuronal apoptosis by inhibiting Gal-3 following ischemic stroke. Biol Proced Online. 25:302023. View Article : Google Scholar : PubMed/NCBI | |
|
Qi J, Han B, Wang Z, Jing L, Tian X and Sun J: Chuanzhitongluo inhibits neuronal apoptosis in mice with acute ischemic stroke by regulating the PI3K/AKT signaling pathway. Neuroscience. 537:21–31. 2024. View Article : Google Scholar | |
|
Xu Z, Li Y, Pi P, Yi Y, Tang H, Zhang Z, Xiong H, Lei B, Shi Y, Li J and Sun Z: B. glomerulata promotes neuroprotection against ischemic stroke by inhibiting apoptosis through the activation of PI3K/AKT/mTOR pathway. Phytomedicine. 132:1558172024. View Article : Google Scholar : PubMed/NCBI | |
|
Meffert MK and Baltimore D: Physiological functions for brain NF-kappaB. Trends Neurosci. 28:37–43. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Baltimore D: Discovering NF-kappaB. Cold Spring Harb Perspect Biol. 1:a0000262009. View Article : Google Scholar | |
|
Zhang Q, Lenardo MJ and Baltimore D: 30 Years of NF-κB: A blossoming of relevance to human pathobiology. Cell. 168:37–57. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Li R, Zhou Y, Zhang S, Li J, Zheng Y and Fan X: The natural (poly)phenols as modulators of microglia polarization via TLR4/NF-κB pathway exert anti-inflammatory activity in ischemic stroke. Eur J Pharmacol. 914:1746602022. View Article : Google Scholar | |
|
Yang CH, Yen TL, Hsu CY, Thomas PA, Sheu JR and Jayakumar T: Multi-targeting andrographolide, a novel NF-κB inhibitor, as a potential therapeutic agent for stroke. Int J Mol Sci. 18:16382017. View Article : Google Scholar | |
|
Zhou H, Yang WS, Li Y, Ren T, Peng L, Guo H, Liu JF, Zhou Y, Zhao Y, Yang LC and Jin X: Oleoylethanolamide attenuates apoptosis by inhibiting the TLR4/NF-κB and ERK1/2 signaling pathways in mice with acute ischemic stroke. Naunyn Schmiedebergs Arch Pharmacol. 390:77–84. 2017. View Article : Google Scholar | |
|
Yan L and Zhu T: Effects of rosuvastatin on neuronal apoptosis in cerebral ischemic stroke rats via Sirt1/NF-kappa B signaling pathway. Eur Rev Med Pharmacol Sci. 23:5449–5455. 2019.PubMed/NCBI | |
|
Li R, Si M, Jia HY, Ma Z, Li XW, Li XY, Dai XR, Gong P and Luo SY: Anfibatide alleviates inflammation and apoptosis via inhibiting NF-kappaB/NLRP3 axis in ischemic stroke. Eur J Pharmacol. 926:1750322022. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Wu H, Han Z, Sheng H, Wu Y and Wang Y, Guo X, Zhu Y, Li X and Wang Y: Guhong injection promotes post-stroke functional recovery via attenuating cortical inflammation and apoptosis in subacute stage of ischemic stroke. Phytomedicine. 99:1540342022. View Article : Google Scholar : PubMed/NCBI | |
|
Zheng Z, Hou F, He G, Jiang F, Bao X and Tong M: Carvedilol reduces the neuronal apoptosis after ischemic stroke by modulating activator of transcription 3 expression in vitro. Dev Neurosci. 45:94–104. 2023. View Article : Google Scholar | |
|
Xu Y, Wang Y, Wang G, Ye X, Zhang J, Cao G, Zhao Y, Gao Z, Zhang Y, Yu B and Kou J: YiQiFuMai powder injection protects against ischemic stroke via inhibiting neuronal apoptosis and PKCδ/Drp1-mediated excessive mitochondrial fission. Oxid Med Cell Longev. 2017:18320932017. View Article : Google Scholar | |
|
Qiu J, Wang X, Wu F, Wan L, Cheng B, Wu Y and Bai B: Low dose of apelin-36 attenuates ER stress-associated apoptosis in rats with ischemic stroke. Front Neurol. 8:5562017. View Article : Google Scholar : PubMed/NCBI | |
|
Wu F, Qiu J, Fan Y, Zhang Q, Cheng B, Wu Y and Bai B: Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating Gα(i)/Gα(q)-CK2 signaling in ischemic stroke. Exp Neurol. 302:136–144. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Li F, Zhao H, Han Z, Wang R, Tao Z, Fan Z, Zhang S, Li G, Chen Z and Luo Y: Xuesaitong may protect against ischemic stroke by modulating microglial phenotypes and inhibiting neuronal cell apoptosis via the STAT3 signaling pathway. CNS Neurol Disord Drug Targets. 18:115–123. 2019. View Article : Google Scholar | |
|
Li HQ, Xia SN, Xu SY, Liu PY, Gu Y, Bao XY, Xu Y and Cao X: γ-glutamylcysteine alleviates ischemic stroke-induced neuronal apoptosis by inhibiting ROS-mediated endoplasmic reticulum stress. Oxid Med Cell Longev. 2021:29610792021. View Article : Google Scholar | |
|
Joshi B, Singh D, Wasan H, Sharma U and Reeta KH: Tideglusib ameliorates ischemia/reperfusion damage by inhibiting GSK-3β and apoptosis in rat model of ischemic stroke. J Stroke Cerebrovasc Dis. 31:1063492022. View Article : Google Scholar | |
|
Ding Y, Lang Y, Zhang H, Li Y, Liu X and Li M: Candesartan reduces neuronal apoptosis caused by ischemic stroke via regulating the FFAR1/ITGA4 pathway. Mediators Inflamm. 2022:23565072022. View Article : Google Scholar : PubMed/NCBI | |
|
Li L, Song JJ, Zhang MX, Zhang HW, Zhu HY, Guo W, Pan CL, Liu X, Xu L and Zhang ZY: Oridonin ameliorates caspase-9-mediated brain neuronal apoptosis in mouse with ischemic stroke by inhibiting RIPK3-mediated mitophagy. Acta Pharmacol Sin. 44:726–740. 2023. View Article : Google Scholar : | |
|
Zhang L, Zhou T, Ji Q, He L, Lan Y, Ding L, Li L and Wang Z: Myricetin improves apoptosis after ischemic stroke via inhibiting MAPK-ERK pathway. Mol Biol Rep. 50:2545–2557. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Shi GS, Qin QL, Huang C, Li ZR, Wang ZH, Wang YY, He XY and Zhao XM: The pathological mechanism of neuronal autophagy-lysosome dysfunction after ischemic stroke. Cell Mol Neurobiol. 43:3251–3263. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang J, Dai J and Cui H: Vitexin reverses the autophagy dysfunction to attenuate MCAO-induced cerebral ischemic stroke via mTOR/Ulk1 pathway. Biomed Pharmacother. 99:583–590. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Tang T, Gao D, Yang X, Hua X, Li S and Sun H: Exogenous netrin-1 inhibits autophagy of ischemic brain tissues and hypoxic neurons via PI3K/mTOR pathway in ischemic stroke. J Stroke Cerebrovasc Dis. 28:1338–1345. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, He Q, Yang M, Hua S, Ma Q, Guo L, Wu X, Zhang C, Fu X and Liu J: Dichloromethane extraction from Piper nigrum L. and P. longum L. to mitigate ischemic stroke by activating the AKT/mTOR signaling pathway to suppress autophagy. Brain Res. 1749:1470472020. View Article : Google Scholar : PubMed/NCBI | |
|
Liu M, Li Y, Han S, Wang H and Li J: Activin A alleviates neuronal injury through inhibiting cGAS-STING-mediated autophagy in mice with ischemic stroke. J Cereb Blood Flow Metab. 43:736–748. 2023. View Article : Google Scholar : | |
|
Lv S, Geng X, Yun HJ and Ding Y: Phenothiazines reduced autophagy in ischemic stroke through endoplasmic reticulum (ER) stress-associated PERK-eIF2α pathway. Exp Neurol. 369:1145242023. View Article : Google Scholar | |
|
Yuan Q, Ren H, Lu J, Yang M, Xie Z, Ma B, Ma L, Fu X, Liu J and Zhang Y: Effects of dichloromethane extraction from Piper nigrum L. and P. longum L. on the expression of autophagy-related proteins in ischemic stroke. J Chem Neuroanat. 127:1022012023. View Article : Google Scholar | |
|
Zhu Y, Yu J, Gong J, Shen J, Ye D, Cheng D, Xie Z, Zeng J, Xu K, Shen J, et al: PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia. Aging (Albany NY). 13:3405–3427. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Wang Y, Guan X, Gao CL, Ruan W, Zhao S, Kai G, Li F and Pang T: Medioresinol as a novel PGC-1α activator prevents pyroptosis of endothelial cells in ischemic stroke through PPARα-GOT1 axis. Pharmacol Res. 169:1056402021. View Article : Google Scholar | |
|
Xia Y, Ling X, Hu G, Zhu Q, Zhang J, Li Q, Zhao B, Wang Y and Deng Z: Small extracellular vesicles secreted by human iPSC-derived MSC enhance angiogenesis through inhibiting STAT3-dependent autophagy in ischemic stroke. Stem Cell Res Ther. 11:3132020. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Liu Y, Cui Q, Fu Z, Yu H, Liu A, Liu J, Qin X, Ge S and Zhang G: Hydroxysafflor yellow A Alleviates ischemic stroke in rats via HIF-1[Formula: See text], BNIP3, and Notch1-mediated inhibition of autophagy. Am J Chin Med. 50:799–815. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Nabavi SF, Sureda A, Sanches-Silva A, Pandima Devi K, Ahmed T, Shahid M, Sobarzo-Sánchez E, Dacrema M, Daglia M, Braidy N, et al: Novel therapeutic strategies for stroke: The role of autophagy. Crit Rev Clin Lab Sci. 56:182–199. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Li Y, Hu K, Liang M, Yan Q, Huang M, Jin L, Chen Y, Yang X and Li X: Stilbene glycoside upregulates SIRT3/AMPK to promotes neuronal mitochondrial autophagy and inhibit apoptosis in ischemic stroke. Adv Clin Exp Med. 30:139–146. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ao LY, Li WT, Zhou L, Yan YY, Ye AQ, Liang BW, Shen WY, Zhu X and Li YM: Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy via AMPK-ULK1 signaling pathway in rats. Brain Res Bull. 153:162–170. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Li X, Zhang D, Bai Y, Xiao J, Jiao H and He R: Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis. Neuropsychiatr Dis Treat. 15:1813–1822. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhou S, Qiao B, Chu X and Kong Q: Oxymatrine attenuates cognitive deficits through SIRT1-mediated autophagy in ischemic stroke. J Neuroimmunol. 323:136–142. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Li H, Zhao Y, Zhao T, Wang Z and Tang Q: Neuronal injury after ischemic stroke: Mechanisms of crosstalk involving necroptosis. J Mol Neurosci. 75:152025. View Article : Google Scholar : PubMed/NCBI | |
|
Deng XX, Li SS and Sun FY: Necrostatin-1 prevents necroptosis in brains after ischemic stroke via inhibition of RIPK1-mediated RIPK3/MLKL signaling. Aging Dis. 10:807–817. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang YY, Liu WN, Li YQ, Zhang XJ, Yang J, Luo XJ and Peng J: Ligustroflavone reduces necroptosis in rat brain after ischemic stroke through targeting RIPK1/RIPK3/MLKL pathway. Naunyn Schmiedebergs Arch Pharmacol. 392:1085–1095. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang YY, Tian J, Peng ZM, Liu B, Peng YW, Zhang XJ, Hu ZY, Luo XJ and Peng J: Caspofungin suppresses brain cell necroptosis in ischemic stroke rats via up-regulation of pellino3. Cardiovasc Drugs Ther. 37:9–23. 2023. View Article : Google Scholar | |
|
Zhang YY, Peng JJ, Chen D, Liu HQ, Yao BF, Peng J and Luo XJ: Telaprevir improves memory and cognition in mice suffering ischemic stroke via targeting MALT1-mediated calcium overload and necroptosis. ACS Chem Neurosci. 14:3113–3124. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Li L, Shi C, Dong F, Xu G, Lei M and Zhang F: Targeting pyroptosis to treat ischemic stroke: From molecular pathways to treatment strategy. Int Immunopharmacol. 133:1121682024. View Article : Google Scholar : PubMed/NCBI | |
|
Wang M, Liu Z, Hu S, Duan X, Zhang Y, Peng C, Peng D and Han L: Taohong siwu decoction ameliorates ischemic stroke injury via suppressing pyroptosis. Front Pharmacol. 11:5904532020. View Article : Google Scholar | |
|
Ran Y, Su W, Gao F, Ding Z, Yang S, Ye L, Chen X, Tian G, Xi J and Liu Z: Curcumin ameliorates white matter injury after ischemic stroke by inhibiting microglia/macrophage pyroptosis through NF-κB suppression and NLRP3 inflammasome inhibition. Oxid Med Cell Longev. 2021:15521272021. View Article : Google Scholar | |
|
Li F, Xu D, Hou K, Gou X, Lv N, Fang W and Li Y: Pretreatment of indobufen and aspirin and their combinations with clopidogrel or ticagrelor alleviates inflammasome mediated pyroptosis via inhibiting NF-κB/NLRP3 pathway in ischemic stroke. J Neuroimmune Pharmacol. 16:835–853. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Ge Y, Wang L, Wang C, Chen J, Dai M, Yao S and Lin Y: CX3CL1 inhibits NLRP3 inflammasome-induced microglial pyroptosis and improves neuronal function in mice with experimentally-induced ischemic stroke. Life Sci. 300:1205642022. View Article : Google Scholar : PubMed/NCBI | |
|
Hu R, Liang J, Ding L, Zhang W, Liu X, Song B and Xu Y: Edaravone dexborneol provides neuroprotective benefits by suppressing NLRP3 inflammasome-induced microglial pyroptosis in experimental ischemic stroke. Int Immunopharmacol. 113(Pt A): 1093152022. View Article : Google Scholar : PubMed/NCBI | |
|
Long J, Sun Y, Liu S, Chen C, Yan Q, Lin Y, Zhang Z, Chu S, Yang Y, Yang S, et al: Ginsenoside Rg1 treats ischemic stroke by regulating CKLF1/CCR5 axis-induced neuronal cell pyroptosis. Phytomedicine. 123:1552382024. View Article : Google Scholar | |
|
Zhou M, Zhang T, Zhang B, Zhang X, Gao S, Zhang T, Li S, Cai X and Lin Y: A DNA nanostructure-based neuroprotectant against neuronal apoptosis via inhibiting toll-like receptor 2 signaling pathway in acute ischemic stroke. ACS Nano. 16:1456–1470. 2022. View Article : Google Scholar | |
|
Wang Y, Yuan H, Shen D, Liu S, Kong W, Zheng K, Yang J and Ge L: Artemisinin attenuated ischemic stroke induced pyroptosis by inhibiting ROS/TXNIP/NLRP3/Caspase-1 signaling pathway. Biomed Pharmacother. 177:1168942024. View Article : Google Scholar : PubMed/NCBI | |
|
Alattar A, Alshaman R, Althobaiti YS, Soliman GM, Ali HS, Khubrni WS, Koh PO, Rehman NU and Shah FA: Quercetin alleviated inflammasome-mediated pyroptosis and modulated the mTOR/P70S6/P6/eIF4E/4EBP1 pathway in ischemic stroke. Pharmaceuticals (Basel). 16:11822023. View Article : Google Scholar : PubMed/NCBI | |
|
Yu X, Wang S, Wang X, Li Y and Dai Z: Melatonin improves stroke by inhibiting autophagy-dependent ferroptosis mediated by NCOA4 binding to FTH1. Exp Neurol. 379:1148682024. View Article : Google Scholar : PubMed/NCBI | |
|
Jia CL, Gou Y, Gao Y, Pei X, Jin X, Li BL, Zhang Z, He Y, Ji ES and Zhao Y: Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs. Phytomedicine. 132:1558352024. View Article : Google Scholar : PubMed/NCBI | |
|
Sun J, Zhao K, Zhang W, Guo C and Liu H: Ecdysterone improves oxidative damage induced by acute ischemic stroke via inhibiting ferroptosis in neurons through ACSL4. J Ethnopharmacol. 331:1182042024. View Article : Google Scholar : PubMed/NCBI | |
|
Sun Y, Jin H, He J, Lai J, Lin H and Liu X: Melatonin alleviates ischemic stroke by inhibiting ferroptosis through the CYP1B1/ACSL4 pathway. Environ Toxicol. 39:2623–2633. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Jin Z, Gao W, Guo F, Liao S, Hu M, Yu T, Yu S and Shi Q: Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating fat mass and obesity-associated-N6-methyladenosine-acyl-CoA synthetase long-chain family member 4 axis. J Neurochem. 166:328–345. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Kajarabille N and Latunde-Dada GO: Programmed cell-death by ferroptosis: Antioxidants as mitigators. Int J Mol Sci. 20:49682019. View Article : Google Scholar : PubMed/NCBI | |
|
Liu C, Liu E, Li Z, Li W, Jin J, Sui H, Chen G, Sun Z and Xi H: Danlou tablet attenuates ischemic stroke injury and blood-brain barrier damage by inhibiting ferroptosis. J Ethnopharmacol. 322:1176572024. View Article : Google Scholar | |
|
Bai X, Zheng E, Tong L, Liu Y, Li X and Yang H, Jiang J, Chang Z and Yang H: Angong Niuhuang Wan inhibit ferroptosis on ischemic and hemorrhagic stroke by activating PPARγ/AKT/GPX4 pathway. J Ethnopharmacol. 321:1174382024. View Article : Google Scholar | |
|
Zhan S, Liang J, Lin H, Cai J, Yang X, Wu H, Wei J, Wang S and Xian M: SATB1/SLC7A11/HO-1 axis ameliorates ferroptosis in neuron cells after ischemic stroke by danhong injection. Mol Neurobiol. 60:413–427. 2023. View Article : Google Scholar | |
|
Li XN, Shang NY, Kang YY, Sheng N, Lan JQ, Tang JS, Wu L, Zhang JL and Peng Y: Caffeic acid alleviates cerebral ischemic injury in rats by resisting ferroptosis via Nrf2 signaling pathway. Acta Pharmacol Sin. 45:248–267. 2024. View Article : Google Scholar : | |
|
Peng C, Ai Q, Zhao F, Li H, Sun Y, Tang K, Yang Y, Chen N and Liu F: Quercetin attenuates cerebral ischemic injury by inhibiting ferroptosis via Nrf2/HO-1 signaling pathway. Eur J Pharmacol. 963:1762642024. View Article : Google Scholar | |
|
Mi Y, Wang Y, Liu Y, Dang W, Xu L, Tan S, Liu L, Chen G, Liu Y, Li N and Hou Y: Kellerin alleviates cerebral ischemic injury by inhibiting ferroptosis via targeting Akt-mediated transcriptional activation of Nrf2. Phytomedicine. 128:1554062024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Ye P, Zhu H, Gu L, Li Y, Feng S, Zeng Z, Chen Q, Zhou B and Xiong X: Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway. CNS Neurosci Ther. 30:e144562024. View Article : Google Scholar | |
|
Wu C, Duan F, Yang R, Dai Y, Chen X and Li S: 15, 16-Dihydrotanshinone I protects against ischemic stroke by inhibiting ferroptosis via the activation of nuclear factor erythroid 2-related factor 2. Phytomedicine. 114:1547902023. View Article : Google Scholar : PubMed/NCBI | |
|
Duan WL, Ma YP, Wang XJ, Ma CS, Han B, Sheng ZM, Dong H, Zhang LY, Li PA, Zhang BG and He MT: N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis. Eur J Pharmacol. 972:1765532024. View Article : Google Scholar : PubMed/NCBI | |
|
Zhu F, Ding S, Liu Y, Wang X and Wu Z: Ozone-mediated cerebral protection: Unraveling the mechanism through ferroptosis and the NRF2/SLC7A11/GPX4 signaling pathway. J Chem Neuroanat. 136:1023872024. View Article : Google Scholar : PubMed/NCBI | |
|
Xiao P, Huang H, Zhao H, Liu R, Sun Z, Liu Y, Chen N and Zhang Z: Edaravone dexborneol protects against cerebral ischemia/reperfusion-induced blood-brain barrier damage by inhibiting ferroptosis via activation of nrf-2/HO-1/GPX4 signaling. Free Radic Biol Med. 217:116–125. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Hu S, Fei Y, Jin C, Yao J, Ding H, Wang J and Liu C: Ginsenoside Rd enhances blood-brain barrier integrity after cerebral ischemia/reperfusion by alleviating endothelial cells ferroptosis via activation of N RG1/ ErbB4 -mediated PI3K /A kt /mTOR signaling pathway. Neuropharmacology. 251:1099292024. View Article : Google Scholar | |
|
Li Y, Sun Y, Wang J, Wang X and Yang W: Voacangine protects hippocampal neuronal cells against oxygen-glucose deprivation/reoxygenation-caused oxidative stress and ferroptosis by activating the PI3K-Akt-FoxO signaling. J Appl Toxicol. 44:1246–1256. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Hilkens NA, Casolla B, Leung TW and de Leeuw FE: Stroke. Lancet. 403:2820–2836. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Yuan J and Ofengeim D: A guide to cell death pathways. Nat Rev Mol Cell Biol. 25:379–395. 2024. View Article : Google Scholar | |
|
Tian X, Li X, Pan M, Yang LZ, Li Y and Fang W: Progress of ferroptosis in ischemic stroke and therapeutic targets. Cell Mol Neurobiol. 44:252024. View Article : Google Scholar : PubMed/NCBI | |
|
Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD, et al: Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 375:1254–1261. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Candelario-Jalil E, Dijkhuizen RM and Magnus T: Neuroinflammation, stroke, blood-brain barrier dysfunction, and imaging modalities. Stroke. 53:1473–1486. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Liang Z, Lou Y, Hao Y, Li H, Feng J and Liu S: The relationship of astrocytes and microglia with different stages of ischemic stroke. Curr Neuropharmacol. 21:2465–2480. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Qin C, Zhou LQ, Ma XT, Hu ZW, Yang S, Chen M, Bosco DB, Wu LJ and Tian DS: Dual functions of microglia in ischemic stroke. Neurosci Bull. 35:921–933. 2019. View Article : Google Scholar : PubMed/NCBI | |
|
Sun X, Yang Y, Meng X, Li J, Liu X and Liu H: PANoptosis: Mechanisms, biology, and role in disease. Immunol Rev. 321:246–262. 2024. View Article : Google Scholar | |
|
Tian HY, Lei YX, Zhou JT, Liu LJ, Yang T, Zhou Y, Ge JW, Xu C and Mei ZG: Insight into interplay between PANoptosis and autophagy: novel therapeutics in ischemic stroke. Front Mol Neurosci. 17:14820152024. View Article : Google Scholar |
