Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis: A Novel Therapeutic Target in Nervous System Diseases
Abstract
:1. Introduction
2. Ferroptosis
2.1. Definition
2.2. Mechanism
2.2.1. System Xc-/GPX4
2.2.2. FSP1-COQ10 Pathway
2.2.3. P62-Keap1-NRF2 Pathway
2.2.4. Iron Accumulation
3. Necroptosis
The Definition and Mechanism of Necroptosis
4. Pyroptosis
The Definition and Mechanism of Pyroptosis
5. These Three Types of Cell Deaths Are Different from Apoptosis
6. Association of Cell Death with Neurodegenerative Diseases
6.1. Ferroptosis and Neurodegenerative Diseases
6.1.1. Ferroptosis and Parkinson’s Disease
6.1.2. Ferroptosis and Alzheimer’s Disease
6.1.3. Ferroptosis and Huntington’s Disease
6.2. Necroptosis and Neurodegenerative Diseases
6.2.1. Necroptosis and Parkinson’s Disease
6.2.2. Necroptosis and Alzheimer’s Disease
6.2.3. Necroptosis and Huntington’s Disease
6.3. Pyroptosis and Neurodegenerative Diseases
6.3.1. Pyroptosis and Parkinson’s Disease
6.3.2. Pyroptosis and Alzheimer’s Disease
6.3.3. Pyroptosis and Huntington’s Disease
7. Association of Cell Death with Traumatic Brain Injury
7.1. Ferroptosis and Traumatic Brain Injury
7.2. Necroptosis and Traumatic Brain Injury
7.3. Pyroptosis and Traumatic Brain Injury
8. Association of Cell Death with Stroke
8.1. Ferroptosis and Stroke
8.2. Necroptosis and Stroke
8.3. Pyroptosis and Stroke
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Galluzzi, L.; Vitale, I.; Aaronson, S.A.; Abrams, J.M.; Adam, D.; Agostinis, P.; Alnemri, E.S.; Altucci, L.; Amelio, I.; Andrews, D.W.; et al. Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018, 25, 486–541. [Google Scholar] [CrossRef] [PubMed]
- Miao, Y.-D.; Quan, W.; Dong, X.; Gan, J.; Ji, C.-F.; Wang, J.-T.; Zhang, F. A Bibliometric Analysis of Ferroptosis, Necroptosis, Pyroptosis, and Cuproptosis in Cancer from 2012 to 2022. Cell Death Discov. 2023, 9, 129. [Google Scholar] [CrossRef] [PubMed]
- Tang, R.; Xu, J.; Zhang, B.; Liu, J.; Liang, C.; Hua, J.; Meng, Q.; Yu, X.; Shi, S. Ferroptosis, Necroptosis, and Pyroptosis in Anticancer Immunity. J. Hematol. Oncol. 2020, 13, 110. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Li, Y. The Interaction between Ferroptosis and Lipid Metabolism in Cancer. Signal Transduct. Target. Ther. 2020, 5, 108. [Google Scholar] [CrossRef]
- Dixon, S.J.; Lemberg, K.M.; Lamprecht, M.R.; Skouta, R.; Zaitsev, E.M.; Gleason, C.E.; Patel, D.N.; Bauer, A.J.; Cantley, A.M.; Yang, W.S.; et al. Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell 2012, 149, 1060–1072. [Google Scholar] [CrossRef]
- Yagoda, N.; Von Rechenberg, M.; Zaganjor, E.; Bauer, A.J.; Yang, W.S.; Fridman, D.J.; Wolpaw, A.J.; Smukste, I.; Peltier, J.M.; Boniface, J.J.; et al. Ras-Raf-Mek-Dependent Oxidative Cell Death Involving Voltage-Dependent Anion Channels. Nature 2007, 447, 864–868. [Google Scholar] [CrossRef]
- Friedmann Angeli, J.P.; Schneider, M.; Proneth, B.; Tyurina, Y.Y.; Tyurin, V.A.; Hammond, V.J.; Herbach, N.; Aichler, M.; Walch, A.; Eggenhofer, E.; et al. Inactivation of the Ferroptosis Regulator Gpx4 Triggers Acute Renal Failure in Mice. Nat. Cell Biol. 2014, 16, 1180–1191. [Google Scholar] [CrossRef]
- Purnama, C.A.; Meiliana, A.; Barliana, M.I.; Lestari, K. Update of Cellular Responses to the Efferocytosis of Necroptosis and Pyroptosis. Cell Div. 2023, 18, 5. [Google Scholar] [CrossRef]
- Micheau, O.; Tschopp, J. Induction of Tnf Receptor I-Mediated Apoptosis via Two Sequential Signaling Complexes. Cell 2003, 114, 181–190. [Google Scholar] [CrossRef]
- Amin, P.; Florez, M.; Najafov, A.; Pan, H.; Geng, J.; Ofengeim, D.; Dziedzic, S.A.; Wang, H.; Barrett, V.J.; Ito, Y.; et al. Regulation of a Distinct Activated Ripk1 Intermediate Bridging Complex I and Complex Ii in Tnfα-Mediated Apoptosis. Proc. Natl. Acad. Sci. USA 2018, 115, E5944–E5953. [Google Scholar] [CrossRef]
- Vanden Berghe, T.; Linkermann, A.; Jouan-Lanhouet, S.; Walczak, H.; Vandenabeele, P. Regulated Necrosis: The Expanding Network of Non-Apoptotic Cell Death Pathways. Nat. Rev. Mol. Cell Biol. 2014, 15, 135–147. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Liu, C. Better Together: A Hybrid Amyloid Signals Necroptosis. Cell 2018, 173, 1068–1070. [Google Scholar] [CrossRef] [PubMed]
- Mompeán, M.; Li, W.; Li, J.; Laage, S.; Siemer, A.B.; Bozkurt, G.; Wu, H.; McDermott, A.E. The Structure of the Necrosome Ripk1-Ripk3 Core, a Human Hetero-Amyloid Signaling Complex. Cell 2018, 173, 1244–1253.e10. [Google Scholar] [CrossRef] [PubMed]
- Yang, B.; Zhong, W.; Gu, Y.; Li, Y. Emerging Mechanisms and Targeted Therapy of Pyroptosis in Central Nervous System Trauma. Front. Cell Dev. Biol. 2022, 10, 832114. [Google Scholar] [CrossRef]
- Shi, J.; Zhao, Y.; Wang, K.; Shi, X.; Wang, Y.; Huang, H.; Zhuang, Y.; Cai, T.; Wang, F.; Shao, F. Cleavage of Gsdmd by Inflammatory Caspases Determines Pyroptotic Cell Death. Nature 2015, 526, 660–665. [Google Scholar] [CrossRef]
- Shi, J.; Gao, W.; Shao, F. Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem. Sci. 2017, 42, 245–254. [Google Scholar] [CrossRef]
- Hu, X.; Chen, H.; Xu, H.; Wu, Y.; Wu, C.; Jia, C.; Li, Y.; Sheng, S.; Xu, C.; Xu, H.; et al. Role of Pyroptosis in Traumatic Brain and Spinal Cord Injuries. Int. J. Biol. Sci. 2020, 16, 2042–2050. [Google Scholar] [CrossRef]
- Dai, X.; Wang, D.; Zhang, J. Programmed Cell Death, Redox Imbalance, and Cancer Therapeutics. Apoptosis Int. J. Program. Cell Death 2021, 26, 385–414. [Google Scholar] [CrossRef]
- Li, J.; Cao, F.; Yin, H.; Huang, Z.; Lin, Z.; Mao, N.; Sun, B.; Wang, G. Ferroptosis: Past, Present and Future. Cell Death Dis. 2020, 11, 88. [Google Scholar] [CrossRef]
- Yao, M.-Y.; Liu, T.; Zhang, L.; Wang, M.-J.; Yang, Y.; Gao, J. Role of Ferroptosis in Neurological Diseases. Neurosci. Lett. 2021, 747, 135614. [Google Scholar] [CrossRef]
- Li, S.; Wang, M.; Wang, Y.; Guo, Y.; Tao, X.; Wang, X.; Cao, Y.; Tian, S.; Li, Q. P53-Mediated Ferroptosis Is Required for 1-Methyl-4-Phenylpyridinium-Induced Senescence of Pc12 Cells. Toxicol. Vitr. Int. J. Publ. Assoc. BIBRA 2021, 73, 105146. [Google Scholar] [CrossRef] [PubMed]
- Gnanapradeepan, K.; Basu, S.; Barnoud, T.; Budina-Kolomets, A.; Kung, C.-P.; Murphy, M.E. The P53 Tumor Suppressor in the Control of Metabolism and Ferroptosis. Front. Endocrinol. 2018, 9, 124. [Google Scholar] [CrossRef] [PubMed]
- Jiang, L.; Kon, N.; Li, T.; Wang, S.-J.; Su, T.; Hibshoosh, H.; Baer, R.; Gu, W. Ferroptosis as a P53-Mediated Activity During Tumour Suppression. Nature 2015, 520, 57–62. [Google Scholar] [CrossRef] [PubMed]
- Seiler, A.; Schneider, M.; Förster, H.; Roth, S.; Wirth, E.K.; Culmsee, C.; Plesnila, N.; Kremmer, E.; Rådmark, O.; Wurst, W.; et al. Glutathione Peroxidase 4 Senses and Translates Oxidative Stress into 12/15-Lipoxygenase Dependent- and Aif-Mediated Cell Death. Cell Metab. 2008, 8, 237–248. [Google Scholar] [CrossRef]
- Cao, J.Y.; Dixon, S.J. Mechanisms of Ferroptosis. Cell Mol. Life Sci. CMLS 2016, 73, 2195–2209. [Google Scholar] [CrossRef]
- Bersuker, K.; Hendricks, J.M.; Li, Z.; Magtanong, L.; Ford, B.; Tang, P.H.; Roberts, M.A.; Tong, B.; Maimone, T.J.; Zoncu, R.; et al. The Coq Oxidoreductase Fsp1 Acts Parallel to Gpx4 to Inhibit Ferroptosis. Nature 2019, 575, 688–692. [Google Scholar] [CrossRef]
- Sun, X.; Ou, Z.; Chen, R.; Niu, X.; Chen, D.; Kang, R.; Tang, D. Activation of the P62-Keap1-Nrf2 Pathway Protects against Ferroptosis in Hepatocellular Carcinoma Cells. Hepatology 2015, 63, 173–184. [Google Scholar] [CrossRef]
- Chen, W.; Xie, L.; Lv, C.; Song, E.; Zhu, X.; Song, Y. Transferrin-Targeted Cascade Nanoplatform for Inhibiting Transcription Factor Nuclear Factor Erythroid 2-Related Factor 2 and Enhancing Ferroptosis Anticancer Therapy. ACS Appl. Mater. Interfaces 2023, 10, 1021. [Google Scholar] [CrossRef]
- Geng, Z.; Guo, Z.; Guo, R.; Ye, R.; Zhu, W.; Yan, B. Ferroptosis and Traumatic Brain Injury. Brain Res. Bull. 2021, 172, 212–219. [Google Scholar] [CrossRef]
- Thomas, C.; Mackey, M.M.; Diaz, A.A.; Cox, D.P. Hydroxyl Radical Is Produced via the Fenton Reaction in Submitochondrial Particles under Oxidative Stress: Implications for Diseases Associated with Iron Accumulation. Redox Rep. Commun. Free Radic. Res. 2009, 14, 102–108. [Google Scholar] [CrossRef]
- Orozco, S.L.; Yatim, N.; Werner, M.R.; Tran, H.; Gunja, S.Y.; Tait, S.W.G.; Albert, M.L.; Green, D.R.; Oberst, A. Ripk1 both Positively and Negatively Regulates Ripk3 Oligomerization and Necroptosis. Cell Death Differ. 2014, 21, 1511–1521. [Google Scholar] [CrossRef] [PubMed]
- Petrie, E.J.; Czabotar, P.E.; Murphy, J.M. The Structural Basis of Necroptotic Cell Death Signaling. Trends Biochem. Sci. 2019, 44, 53–63. [Google Scholar] [CrossRef] [PubMed]
- Degterev, A.; Hitomi, J.; Germscheid, M.; Ch’En, I.L.; Korkina, O.; Teng, X.; Abbott, D.; Cuny, G.D.; Yuan, C.; Wagner, G.; et al. Identification of Rip1 Kinase as a Specific Cellular Target of Necrostatins. Nat. Chem. Biol. 2008, 4, 313–321. [Google Scholar] [CrossRef]
- He, S.; Wang, L.; Miao, L.; Wang, T.; Du, F.; Zhao, L.; Wang, X. Receptor Interacting Protein Kinase-3 Determines Cellular Necrotic Response to Tnf-Alpha. Cell 2009, 137, 1100–1111. [Google Scholar] [CrossRef] [PubMed]
- Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.; Lei, X.; et al. Mixed Lineage Kinase Domain-Like Protein Mediates Necrosis Signaling Downstream of Rip3 Kinase. Cell 2012, 148, 213–227. [Google Scholar] [CrossRef]
- Dhanasekaran, D.N.; Reddy, E.P. Jnk-Signaling: A Multiplexing Hub in Programmed Cell Death. Genes Cancer 2017, 8, 682–694. [Google Scholar] [CrossRef]
- Broz, P.; Dixit, V.M. Inflammasomes: Mechanism of Assembly, Regulation and Signalling. Nat. Reviews. Immunol. 2016, 16, 407–420. [Google Scholar] [CrossRef]
- Aglietti, R.A.; Estevez, A.; Gupta, A.; Ramirez, M.G.; Liu, P.S.; Kayagaki, N.; Ciferri, C.; Dixit, V.M.; Dueber, E.C. Gsdmd P30 Elicited by Caspase-11 during Pyroptosis Forms Pores in Membranes. Proc. Natl. Acad. Sci. USA 2016, 113, 7858–7863. [Google Scholar] [CrossRef]
- Kayagaki, N.; Warming, S.; Lamkanfi, M.; Walle, L.V.; Louie, S.; Dong, J.; Newton, K.; Qu, Y.; Liu, J.; Heldens, S.; et al. Non-Canonical Inflammasome Activation Targets Caspase-11. Nature 2011, 479, 117–121. [Google Scholar] [CrossRef]
- Yu, J.; Nagasu, H.; Murakami, T.; Hoang, H.; Broderick, L.; Hoffman, H.M.; Horng, T. Inflammasome Activation Leads to Caspase-1-Dependent Mitochondrial Damage and Block of Mitophagy. Proc. Natl. Acad. Sci. USA 2014, 111, 15514–15519. [Google Scholar] [CrossRef]
- Kayagaki, N.; Stowe, I.B.; Lee, B.L.; O’Rourke, K.; Anderson, K.; Warming, S.; Cuellar, T.; Haley, B.; Roose-Girma, M.; Phung, Q.T.; et al. Caspase-11 Cleaves Gasdermin D for Non-Canonical Inflammasome Signalling. Nature 2015, 526, 666–671. [Google Scholar] [CrossRef] [PubMed]
- Lučiūnaitė, A.; McManus, R.M.; Jankunec, M.; Rácz, I.; Dansokho, C.; Dalgėdienė, I.; Schwartz, S.; Brosseron, F.; Heneka, M.T. Soluble Aβ Oligomers and Protofibrils Induce Nlrp3 Inflammasome Activation in Microglia. J. Neurochem. 2019, 155, 650–661. [Google Scholar] [CrossRef] [PubMed]
- Muñoz-Planillo, R.; Kuffa, P.; Martínez-Colón, G.; Smith, B.L.; Rajendiran, T.M.; Núñez, G. K⁺ Efflux Is the Common Trigger of Nlrp3 Inflammasome Activation by Bacterial Toxins and Particulate Matter. Immunity 2013, 38, 1142–1153. [Google Scholar] [CrossRef] [PubMed]
- Green, D.R. Apoptotic Pathways: Paper Wraps Stone Blunts Scissors. Cell 2000, 102, 1–4. [Google Scholar] [CrossRef] [PubMed]
- Zhu, P.; Ke, Z.-R.; Chen, J.-X.; Li, S.-J.; Ma, T.-L.; Fan, X.-L. Advances in Mechanism and Regulation of Panoptosis: Prospects in Disease Treatment. Front. Immunol. 2023, 14, 1120034. [Google Scholar] [CrossRef]
- Wang, Y.; Kanneganti, T.-D. From Pyroptosis, Apoptosis and Necroptosis to Panoptosis: A Mechanistic Compendium of Programmed Cell Death Pathways. Comput. Struct. Biotechnol. J. 2021, 19, 4641–4657. [Google Scholar] [CrossRef]
- Ketelut-Carneiro, N.; Fitzgerald, K.A. Apoptosis, Pyroptosis, and Necroptosis-Oh My! The Many Ways a Cell Can Die. J. Mol. Biol. 2021, 434, 167378. [Google Scholar] [CrossRef]
- Elmore, S. Apoptosis: A Review of Programmed Cell Death. Toxicol. Pathol. 2007, 35, 495–516. [Google Scholar] [CrossRef]
- Glass, C.K.; Saijo, K.; Winner, B.; Marchetto, M.C.; Gage, F.H. Mechanisms Underlying Inflammation in Neurodegeneration. Cell 2010, 140, 918–934. [Google Scholar] [CrossRef]
- Dong, X.-X.; Wang, Y.; Qin, Z.-H. Molecular Mechanisms of Excitotoxicity and Their Relevance to Pathogenesis of Neurodegenerative Diseases. Acta Pharmacol. Sin. 2009, 30, 379–387. [Google Scholar] [CrossRef]
- Urrutia, P.J.; Bórquez, D.A.; Núñez, M.T. Inflaming the Brain with Iron. Antioxidants 2021, 10, 61. [Google Scholar] [CrossRef] [PubMed]
- Jenner, P.; Dexter, D.T.; Sian, J.; Schapira, A.H.; Marsden, C.D. Oxidative Stress as a Cause of Nigral Cell Death in Parkinson’s Disease and Incidental Lewy Body Disease. The Royal Kings and Queens Parkinson’s Disease Research Group. Ann. Neurol. 1992, 32, S82–S87. [Google Scholar] [CrossRef] [PubMed]
- Grolez, G.; Moreau, C.; Sablonnière, B.; Garçon, G.; Devedjian, J.-C.; Meguig, S.; Gelé, P.; Delmaire, C.; Bordet, R.; Defebvre, L.; et al. Ceruloplasmin Activity and Iron Chelation Treatment of Patients with Parkinson’s Disease. BMC Neurol. 2015, 15, 74. [Google Scholar] [CrossRef] [PubMed]
- Ashraf, A.; Jeandriens, J.; Parkes, H.G.; So, P.-W. Iron Dyshomeostasis, Lipid Peroxidation and Perturbed Expression of Cystine/Glutamate Antiporter in Alzheimer’s Disease: Evidence of Ferroptosis. Redox Biol. 2020, 32, 101494. [Google Scholar] [CrossRef]
- Mandal, P.K.; Saharan, S.; Tripathi, M.; Murari, G. Brain Glutathione Levels—A Novel Biomarker for Mild Cognitive Impairment and Alzheimer’s Disease. Biol. Psychiatry 2015, 78, 702–710. [Google Scholar] [CrossRef]
- Hambright, W.S.; Fonseca, R.S.; Chen, L.; Na, R.; Ran, Q. Ablation of Ferroptosis Regulator Glutathione Peroxidase 4 in Forebrain Neurons Promotes Cognitive Impairment and Neurodegeneration. Redox Biol. 2017, 12, 8–17. [Google Scholar] [CrossRef]
- van Bergen, J.M.G.; Hua, J.; Unschuld, P.G.; Lim, I.A.L.; Jones, C.K.; Margolis, R.L.; Ross, C.A.; Van Zijl, P.C.M.; Li, X. Quantitative Susceptibility Mapping Suggests Altered Brain Iron in Premanifest Huntington Disease. Am. J. Neuroradiol. 2016, 37, 789–796. [Google Scholar] [CrossRef]
- Quinti, L.; Naidu, S.D.; Träger, U.; Chen, X.; Kegel-Gleason, K.; Llères, D.; Connolly, C.; Chopra, V.; Low, C.; Moniot, S.; et al. Keap1-Modifying Small Molecule Reveals Muted Nrf2 Signaling Responses in Neural Stem Cells from Huntington’s Disease Patients. Proc. Natl. Acad. Sci. USA 2017, 114, E4676–E4685. [Google Scholar] [CrossRef]
- Hu, Y.-B.; Zhang, Y.-F.; Wang, H.; Ren, R.-J.; Cui, H.-L.; Huang, W.-Y.; Cheng, Q.; Chen, H.-Z.; Wang, G. Mir-425 Deficiency Promotes Necroptosis and Dopaminergic Neurodegeneration in Parkinson’s Disease. Cell Death Dis. 2019, 10, 589. [Google Scholar] [CrossRef]
- Iannielli, A.; Bido, S.; Folladori, L.; Segnali, A.; Cancellieri, C.; Maresca, A.; Massimino, L.; Rubio, A.; Morabito, G.; Caporali, L.; et al. Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson’s Disease Models. Cell Rep. 2018, 22, 2066–2079. [Google Scholar] [CrossRef]
- Oñate, M.; Catenaccio, A.; Salvadores, N.; Saquel, C.; Martinez, A.; Moreno-Gonzalez, I.; Gamez, N.; Soto, P.; Soto, C.; Hetz, C.; et al. The Necroptosis Machinery Mediates Axonal Degeneration in a Model of Parkinson Disease. Cell Death Differ. 2020, 27, 1169–1185. [Google Scholar] [CrossRef]
- Koper, M.J.; Van Schoor, E.; Ospitalieri, S.; Vandenberghe, R.; Vandenbulcke, M.; von Arnim, C.A.F.; Tousseyn, T.; Balusu, S.; De Strooper, B.; Thal, D.R. Necrosome Complex Detected in Granulovacuolar Degeneration Is Associated with Neuronal Loss in Alzheimer’s Disease. Acta Neuropathol. 2019, 139, 463–484. [Google Scholar] [CrossRef]
- Park, J.; Ha, H.-J.; Chung, E.S.; Baek, S.H.; Cho, Y.; Kim, H.K.; Han, J.; Sul, J.H.; Lee, J.; Kim, E.; et al. O-Glcnacylation Ameliorates the Pathological Manifestations of Alzheimer’s Disease by Inhibiting Necroptosis. Sci. Adv. 2021, 7, eabd3207. [Google Scholar] [CrossRef]
- Jayaraman, A.; Htike, T.T.; James, R.; Picon, C.; Reynolds, R. Tnf-Mediated Neuroinflammation Is Linked to Neuronal Necroptosis in Alzheimer’s Disease Hippocampus. Acta Neuropathol. Commun. 2021, 9, 159. [Google Scholar] [CrossRef]
- Yang, S.; Lee, D.K.; Shin, J.; Lee, S.; Baek, S.; Kim, J.; Jung, H.; Hah, J.; Kim, Y. Nec-1 Alleviates Cognitive Impairment with Reduction of Aβ and Tau Abnormalities in App/Ps1 Mice. EMBO Mol. Med. 2016, 9, 61–77. [Google Scholar] [CrossRef] [PubMed]
- Zhu, S.; Zhang, Y.; Bai, G.; Li, H. Necrostatin-1 Ameliorates Symptoms in R6/2 Transgenic Mouse Model of Huntington’s Disease. Cell Death Dis. 2011, 2, e115. [Google Scholar] [CrossRef] [PubMed]
- Zhou, Y.; Lu, M.; Du, R.-H.; Qiao, C.; Jiang, C.-Y.; Zhang, K.-Z.; Ding, J.-H.; Hu, G. Microrna-7 Targets Nod-Like Receptor Protein 3 Inflammasome to Modulate Neuroinflammation in the Pathogenesis of Parkinson’s Disease. Mol. Neurodegener. 2016, 11, 28. [Google Scholar] [CrossRef] [PubMed]
- Chatterjee, K.; Roy, A.; Banerjee, R.; Choudhury, S.; Mondal, B.; Halder, S.; Basu, P.; Shubham, S.; Dey, S.; Kumar, H. Inflammasome and A-Synuclein in Parkinson’s Disease: A Cross-Sectional Study. J. Neuroimmunol. 2020, 338, 577089. [Google Scholar] [CrossRef] [PubMed]
- Heneka, M.T.; Kummer, M.P.; Stutz, A.; Delekate, A.; Schwartz, S.; Vieira-Saecker, A.; Griep, A.; Axt, D.; Remus, A.; Tzeng, T.-C.; et al. Nlrp3 Is Activated in Alzheimer’s Disease and Contributes to Pathology in App/Ps1 Mice. Nature 2013, 493, 674–678. [Google Scholar] [CrossRef]
- Han, C.; Yang, Y.; Guan, Q.; Zhang, X.; Shen, H.; Sheng, Y.; Wang, J.; Zhou, X.; Li, W.; Guo, L.; et al. New Mechanism of Nerve Injury in Alzheimer’s Disease: Β-Amyloid-Induced Neuronal Pyroptosis. J. Cell. Mol. Med. 2020, 24, 8078–8090. [Google Scholar] [CrossRef]
- Shen, H.; Han, C.; Yang, Y.; Guo, L.; Sheng, Y.; Wang, J.; Li, W.; Zhai, L.; Wang, G.; Guan, Q. Pyroptosis Executive Protein Gsdmd as a Biomarker for Diagnosis and Identification of Alzheimer’s Disease. Brain Behav. 2021, 11, e02063. [Google Scholar] [CrossRef] [PubMed]
- Paldino, E.; D’angelo, V.; Sancesario, G.; Fusco, F.R. Pyroptotic Cell Death in the R6/2 Mouse Model of Huntington’s Disease: New Insight on the Inflammasome. Cell Death Discov. 2020, 6, 69. [Google Scholar] [CrossRef] [PubMed]
- Chen, K.-P.; Hua, K.-F.; Tsai, F.-T.; Lin, T.-Y.; Cheng, C.-Y.; Yang, D.-I.; Hsu, H.-T.; Ju, T.-C. A Selective Inhibitor of the Nlrp3 Inflammasome as a Potential Therapeutic Approach for Neuroprotection in a Transgenic Mouse Model of Huntington’s Disease. J. Neuroinflamm. 2022, 19, 56. [Google Scholar] [CrossRef] [PubMed]
- Sofic, E.; Riederer, P.; Heinsen, H.; Beckmann, H.; Reynolds, G.P.; Hebenstreit, G.; Youdim, M.B.H. Increased Iron (Iii) and Total Iron Content in Post Mortem Substantia Nigra of Parkinsonian Brain. J. Neural Transm. 1988, 74, 199–205. [Google Scholar] [CrossRef]
- Skouta, R.; Dixon, S.J.; Wang, J.; Dunn, D.E.; Orman, M.; Shimada, K.; Rosenberg, P.A.; Lo, D.C.; Weinberg, J.M.; Linkermann, A.; et al. Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models. J. Am. Chem. Soc. 2014, 136, 4551–4556. [Google Scholar] [CrossRef]
- Zhao, D.; Yang, K.; Guo, H.; Zeng, J.; Wang, S.; Xu, H.; Ge, A.; Zeng, L.; Chen, S.; Ge, J. Mechanisms of Ferroptosis in Alzheimer’s Disease and Therapeutic Effects of Natural Plant Products: A Review. Biomed. Pharmacother. Biomed. Pharmacother. 2023, 164, 114312. [Google Scholar] [CrossRef]
- Zuo, Y.; Xie, J.; Li, X.; Li, Y.; Thirupathi, A.; Zhang, J.; Yu, P.; Gao, G.; Chang, Y.; Shi, Z. Ferritinophagy-Mediated Ferroptosis Involved in Paraquat-Induced Neurotoxicity of Dopaminergic Neurons: Implication for Neurotoxicity in Pd. Oxidative Med. Cell Longev. 2021, 2021, 9961628. [Google Scholar] [CrossRef]
- Speer, R.E.; Karuppagounder, S.S.; Basso, M.; Sleiman, S.F.; Kumar, A.; Brand, D.; Smirnova, N.; Gazaryan, I.; Khim, S.J.; Ratan, R.R. Hypoxia-Inducible Factor Prolyl Hydroxylases as Targets for Neuroprotection by “Antioxidant” Metal Chelators: From Ferroptosis to Stroke. Free Radic. Biol. Med. 2013, 62, 26–36. [Google Scholar] [CrossRef]
- Do Van, B.; Gouel, F.; Jonneaux, A.; Timmerman, K.; Gelé, P.; Pétrault, M.; Bastide, M.; Laloux, C.; Moreau, C.; Bordet, R.; et al. Ferroptosis, a Newly Characterized Form of Cell Death in Parkinson’s Disease That Is Regulated by Pkc. Neurobiol. Dis. 2016, 94, 169–178. [Google Scholar] [CrossRef]
- Quintana, C.; Bellefqih, S.; Laval, J.; Guerquin-Kern, J.; Wu, T.; Avila, J.; Ferrer, I.; Arranz, R.; Patiño, C. Study of the Localization of Iron, Ferritin, and Hemosiderin in Alzheimer’s Disease Hippocampus by Analytical Microscopy at the Subcellular Level. J. Struct. Biol. 2006, 153, 42–54. [Google Scholar] [CrossRef]
- Kim, A.; Lalonde, K.; Truesdell, A.; Gomes Welter, P.; Brocardo, P.S.; Rosenstock, T.R.; Gil-Mohapel, J. New Avenues for the Treatment of Huntington’s Disease. Int. J. Mol. Sci. 2021, 22, 8363. [Google Scholar] [CrossRef] [PubMed]
- Dumas, E.M.; Versluis, M.J.; Bogaard, S.J.V.D.; van Osch, M.J.; Hart, E.P.; van Roon-Mom, W.M.; van Buchem, M.A.; Webb, A.G.; van der Grond, J.; Roos, R.A. Elevated Brain Iron Is Independent from Atrophy in Huntington’s Disease. NeuroImage 2012, 61, 558–564. [Google Scholar] [CrossRef] [PubMed]
- Klepac, N.; Relja, M.; Klepac, R.; Hećimović, S.; Babić, T.; Trkulja, V. Oxidative Stress Parameters in Plasma of Huntington’s Disease Patients, Asymptomatic Huntington’s Disease Gene Carriers and Healthy Subjects: A Cross-Sectional Study. J. Neurol. 2007, 254, 1676–1683. [Google Scholar] [CrossRef]
- Kumar, P.; Kalonia, H.; Kumar, A. Nitric Oxide Mechanism in the Protective Effect of Antidepressants against 3-Nitropropionic Acid-Induced Cognitive Deficit, Glutathione and Mitochondrial Alterations in Animal Model of Huntington’s Disease. Behav. Pharmacol. 2010, 21, 217–230. [Google Scholar] [CrossRef]
- Choo, Y.S.; Mao, Z.; Johnson, G.V.; Lesort, M. Increased Glutathione Levels in Cortical and Striatal Mitochondria of the R6/2 Huntington’s Disease Mouse Model. Neurosci. Lett. 2005, 386, 63–68. [Google Scholar] [CrossRef] [PubMed]
- Chen, C.-M.; Wu, Y.-R.; Cheng, M.-L.; Liu, J.-L.; Lee, Y.-M.; Lee, P.-W.; Soong, B.-W.; Chiu, D.T.-Y. Increased Oxidative Damage and Mitochondrial Abnormalities in the Peripheral Blood of Huntington’s Disease Patients. Biochem. Biophys. Res. Commun. 2007, 359, 335–340. [Google Scholar] [CrossRef]
- del Hoyo, P.; García-Redondo, A.; de Bustos, F.; Molina, J.A.; Sayed, Y.; Alonso-Navarro, H.; Caballero, L.; Arenas, J.; Jiménez-Jiménez, F.J. Oxidative Stress in Skin Fibroblasts Cultures of Patients with Huntington’s Disease. Neurochem. Res. 2006, 31, 1103–1109. [Google Scholar] [CrossRef]
- Lee, J.; Kosaras, B.; Del Signore, S.J.; Cormier, K.; McKee, A.; Ratan, R.R.; Kowall, N.W.; Ryu, H. Modulation of Lipid Peroxidation and Mitochondrial Function Improves Neuropathology in Huntington’s Disease Mice. Acta Neuropathol. 2010, 121, 487–498. [Google Scholar] [CrossRef]
- Xu, Y.; Zhao, J.; Zhao, Y.; Zhou, L.; Qiao, H.; Xu, Q.; Liu, Y. The Role of Ferroptosis in Neurodegenerative Diseases. Mol. Biol. Rep. 2023, 50, 1655–1661. [Google Scholar] [CrossRef]
- Degterev, A.; Ofengeim, D.; Yuan, J. Targeting Ripk1 for the Treatment of Human Diseases. Proc. Natl. Acad. Sci. USA 2019, 116, 9714–9722. [Google Scholar] [CrossRef]
- Caccamo, A.; Branca, C.; Piras, I.S.; Ferreira, E.; Huentelman, M.J.; Liang, W.S.; Readhead, B.; Dudley, J.T.; Spangenberg, E.; Green, K.N.; et al. Necroptosis Activation in Alzheimer’s Disease. Nat. Neurosci. 2017, 20, 1236–1246. [Google Scholar] [CrossRef] [PubMed]
- Salvadores, N.; Moreno-Gonzalez, I.; Gamez, N.; Quiroz, G.; Vegas-Gomez, L.; Escandón, M.; Jimenez, S.; Vitorica, J.; Gutierrez, A.; Soto, C.; et al. Aβ Oligomers Trigger Necroptosis-Mediated Neurodegeneration via Microglia Activation in Alzheimer’s Disease. Acta Neuropathol. Commun. 2022, 10, 31. [Google Scholar] [CrossRef]
- Yuan, J.; Amin, P.; Ofengeim, D. Necroptosis and Ripk1-Mediated Neuroinflammation in Cns Diseases. Nat. Reviews. Neurosci. 2018, 20, 19–33. [Google Scholar] [CrossRef] [PubMed]
- Dhuriya, Y.K.; Sharma, D. Necroptosis: A Regulated Inflammatory Mode of Cell Death. J. Neuroinflamm. 2018, 15, 199. [Google Scholar] [CrossRef] [PubMed]
- Royce, G.H.; Brown-Borg, H.M.; Deepa, S.S. The Potential Role of Necroptosis in Inflammaging and Aging. Geroscience 2019, 41, 795–811. [Google Scholar] [CrossRef]
- Cui, J.; Zhao, S.; Li, Y.; Zhang, D.; Wang, B.; Xie, J.; Wang, J. Regulated Cell Death: Discovery, Features and Implications for Neurodegenerative Diseases. Cell Commun. Signal. 2021, 19, 120. [Google Scholar] [CrossRef]
- Kim, Y.S.; Joh, T.H. Microglia, Major Player in the Brain Inflammation: Their Roles in the Pathogenesis of Parkinson’s Disease. Exp. Mol. Med. 2006, 38, 333–347. [Google Scholar] [CrossRef]
- Codolo, G.; Plotegher, N.; Pozzobon, T.; Brucale, M.; Tessari, I.; Bubacco, L.; de Bernard, M. Triggering of Inflammasome by Aggregated A-Synuclein, an Inflammatory Response in Synucleinopathies. PLoS ONE 2013, 8, e55375. [Google Scholar] [CrossRef]
- Spillantini, M.G.; Schmidt, M.L.; Lee, V.M.-Y.; Trojanowski, J.Q.; Jakes, R.; Goedert, M. Alpha-Synuclein in Lewy Bodies. Nature 1997, 388, 839–840. [Google Scholar] [CrossRef]
- Stancu, I.-C.; Cremers, N.; Vanrusselt, H.; Couturier, J.; Vanoosthuyse, A.; Kessels, S.; Lodder, C.; Brône, B.; Huaux, F.; Octave, J.-N.; et al. Aggregated Tau Activates Nlrp3-Asc Inflammasome Exacerbating Exogenously Seeded and Non-Exogenously Seeded Tau Pathology in Vivo. Acta Neuropathol. 2019, 137, 599–617. [Google Scholar] [CrossRef]
- Cacabelos, R.; Barquero, M.; García, P.; Alvarez, X.A.; de Seijas, E.V. Cerebrospinal Fluid Interleukin-1 Beta (Il-1 Beta) in Alzheimer’s Disease and Neurological Disorders. Methods Find. Exp. Clin. Pharmacol. 1991, 13, 455–458. [Google Scholar] [PubMed]
- Pavlovic, D.; Pekic, S.; Stojanovic, M.; Popovic, V. Traumatic Brain Injury: Neuropathological, Neurocognitive and Neurobehavioral Sequelae. Pituitary 2019, 22, 270–282. [Google Scholar] [CrossRef] [PubMed]
- Corps, K.N.; Roth, T.; McGavern, D.B. Inflammation and Neuroprotection in Traumatic Brain Injury. JAMA Neurol. 2015, 72, 355–362. [Google Scholar] [CrossRef] [PubMed]
- Ng, S.Y.; Lee, A.Y.W. Traumatic Brain Injuries: Pathophysiology and Potential Therapeutic Targets. Front. Cell. Neurosci. 2019, 13, 528. [Google Scholar] [CrossRef]
- Onyszchuk, G.; LeVine, S.M.; Brooks, W.M.; Berman, N.E. Post-Acute Pathological Changes in the Thalamus and Internal Capsule in Aged Mice Following Controlled Cortical Impact Injury: A Magnetic Resonance Imaging, Iron Histochemical, and Glial Immunohistochemical Study. Neurosci. Lett. 2009, 452, 204–208. [Google Scholar] [CrossRef]
- Chen, X.; Gao, C.; Yan, Y.; Cheng, Z.; Chen, G.; Rui, T.; Luo, C.; Gao, Y.; Wang, T.; Chen, X.; et al. Ruxolitinib Exerts Neuroprotection Via Repressing Ferroptosis in a Mouse Model of Traumatic Brain Injury. Exp. Neurol. 2021, 342, 113762. [Google Scholar] [CrossRef]
- Rui, T.; Wang, H.; Li, Q.; Cheng, Y.; Gao, Y.; Fang, X.; Ma, X.; Chen, G.; Gao, C.; Gu, Z.; et al. Deletion of Ferritin H in Neurons Counteracts the Protective Effect of Melatonin against Traumatic Brain Injury-Induced Ferroptosis. J. Pineal Res. 2021, 70, e12704. [Google Scholar] [CrossRef]
- Lin, Y.; Luo, L.L.; Sun, J.; Gao, W.; Tian, Y.; Park, E.; Baker, A.; Chen, J.; Jiang, R.; Zhang, J. Relationship of Circulating Cxcr4 Epc with Prognosis of Mild Traumatic Brain Injury Patients. Aging Dis. 2017, 8, 115–127. [Google Scholar] [CrossRef]
- Xie, B.; Wang, Y.; Lin, Y.; Mao, Q.; Feng, J.; Gao, G.; Jiang, J. Inhibition of Ferroptosis Attenuates Tissue Damage and Improves Long-Term Outcomes after Traumatic Brain Injury in Mice. CNS Neurosci. Ther. 2019, 25, 465–475. [Google Scholar] [CrossRef]
- Anthonymuthu, T.S.; Kenny, E.M.; Lamade, A.M.; Kagan, V.E.; Bayır, H. Oxidized Phospholipid Signaling in Traumatic Brain Injury. Free Radic. Biol. Med. 2018, 124, 493–503. [Google Scholar] [CrossRef]
- Pang, Q.; Zheng, L.; Ren, Z.; Xu, H.; Guo, H.; Shan, W.; Liu, R.; Gu, Z.; Wang, T. Mechanism of Ferroptosis and Its Relationships with Other Types of Programmed Cell Death: Insights for Potential Therapeutic Benefits in Traumatic Brain Injury. Oxidative Med. Cell. Longev. 2022, 2022, 1274550. [Google Scholar] [CrossRef]
- Guerriero, R.M.; Giza, C.C.; Rotenberg, A. Glutamate and Gaba Imbalance Following Traumatic Brain Injury. Curr. Neurol. Neurosci. Rep. 2015, 15, 27. [Google Scholar] [CrossRef] [PubMed]
- Choi, B.Y.; Kim, I.Y.; Kim, J.H.; Lee, B.E.; Lee, S.H.; Kho, A.R.; Jung, H.J.; Sohn, M.; Song, H.K.; Suh, S.W. Decreased Cysteine Uptake by Eaac1 Gene Deletion Exacerbates Neuronal Oxidative Stress and Neuronal Death after Traumatic Brain Injury. Amino Acids 2016, 48, 1619–1629. [Google Scholar] [CrossRef]
- Zhao, P.; Li, C.; Chen, B.; Sun, G.; Chao, H.; Tu, Y.; Bao, Z.; Fan, L.; Du, X.; Ji, J. Up-Regulation of Chmp4b Alleviates Microglial Necroptosis Induced by Traumatic Brain Injury. J. Cell. Mol. Med. 2020, 24, 8466–8479. [Google Scholar] [CrossRef]
- Wehn, A.C.; Khalin, I.; Duering, M.; Hellal, F.; Culmsee, C.; Vandenabeele, P.; Plesnila, N.; Terpolilli, N.A. Ripk1 or Ripk3 Deletion Prevents Progressive Neuronal Cell Death and Improves Memory Function after Traumatic Brain Injury. Acta Neuropathol. Commun. 2021, 9, 138. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.-M.; Chen, Q.-X.; Chen, Z.-B.; Tian, D.-F.; Li, M.-C.; Wang, J.-M.; Wang, L.; Liu, B.-H.; Zhang, S.-Q.; Li, F.; et al. Rip3 Deficiency Protects against Traumatic Brain Injury (Tbi) through Suppressing Oxidative Stress, Inflammation and Apoptosis: Dependent on Ampk Pathway. Biochem. Biophys. Res. Commun. 2018, 499, 112–119. [Google Scholar] [CrossRef] [PubMed]
- Wang, P.; Pan, B.; Tian, J.; Yang, L.; Chen, Z.; Yang, L.; Fan, Z. Ac-Fltd-Cmk Inhibits Pyroptosis and Exerts Neuroprotective Effect in a Mice Model of Traumatic Brain Injury. Neuroreport 2021, 32, 188–197. [Google Scholar] [CrossRef]
- Sun, Z.; Nyanzu, M.; Yang, S.; Zhu, X.; Wang, K.; Ru, J.; Yu, E.; Zhang, H.; Wang, Z.; Shen, J.; et al. Κvx765 Attenuates Pyroptosis and Hmgb1/Tlr4/Nf-B Pathways to Improve Functional Outcomes in Tbi Mice. Oxidative Med. Cell. Longev. 2020, 2020, 7879629. [Google Scholar] [CrossRef]
- Ismael, S.; Nasoohi, S.; Ishrat, T. Mcc950, the Selective Inhibitor of Nucleotide Oligomerization Domain-Like Receptor Protein-3 Inflammasome, Protects Mice against Traumatic Brain Injury. J. Neurotrauma 2018, 35, 1294–1303. [Google Scholar] [CrossRef]
- Chen, T.; Qian, X.; Zhu, J.; Yang, L.-K.; Wang, Y.-H. Controlled Decompression Attenuates Compressive Injury Following Traumatic Brain Injury Via Trek-1-Mediated Inhibition of Necroptosis and Neuroinflammation. Oxidative Med. Cell. Longev. 2021, 2021, 4280951. [Google Scholar] [CrossRef]
- Bao, Z.; Fan, L.; Zhao, L.; Xu, X.; Liu, Y.; Chao, H.; Liu, N.; You, Y.; Liu, Y.; Wang, X.; et al. Silencing of A20 Aggravates Neuronal Death and Inflammation after Traumatic Brain Injury: A Potential Trigger of Necroptosis. Front. Mol. Neurosci. 2019, 12, 222. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.-D.; Li, W.; Chen, Z.-R.; Hu, Y.-C.; Zhang, D.-D.; Shen, W.; Zhou, M.-L.; Zhu, L.; Hang, C.-H. Expression of the Nlrp3 Inflammasome in Cerebral Cortex after Traumatic Brain Injury in a Rat Model. Neurochem. Res. 2013, 38, 2072–2083. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.; Chen, Y.; Meng, J.; Wu, M.; Bi, F.; Chang, C.; Li, H.; Zhang, L. Ablation of Caspase-1 Protects against Tbi-Induced Pyroptosis in Vitro and in Vivo. J. Neuroinflamm. 2018, 15, 48. [Google Scholar] [CrossRef] [PubMed]
- Burdette, B.E.; Esparza, A.N.; Zhu, H.; Wang, S. Gasdermin D in Pyroptosis. Acta Pharm. Sin. B 2021, 11, 2768–2782. [Google Scholar] [CrossRef]
- Ge, X.; Li, W.; Huang, S.; Yin, Z.; Xu, X.; Chen, F.; Kong, X.; Wang, H.; Zhang, J.; Lei, P. The Pathological Role of Nlrs and Aim2 Inflammasome-Mediated Pyroptosis in Damaged Blood-Brain Barrier after Traumatic Brain Injury. Brain Res. 2018, 1697, 10–20. [Google Scholar] [CrossRef]
- Chen, J.; Wang, Y.; Wu, J.; Yang, J.; Li, M.; Chen, Q. The Potential Value of Targeting Ferroptosis in Early Brain Injury after Acute Cns Disease. Front. Mol. Neurosci. 2020, 13, 110. [Google Scholar] [CrossRef]
- Marston, N.A.; Patel, P.N.; Kamanu, F.K.; Nordio, F.; Melloni, G.M.; Roselli, C.; Gurmu, Y.; Weng, L.-C.; Bonaca, M.P.; Giugliano, R.P.; et al. Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients with Cardiometabolic Disease. Circulation 2021, 143, 470–478. [Google Scholar] [CrossRef]
- Morotti, A.; Goldstein, J.N. Diagnosis and Management of Acute Intracerebral Hemorrhage. Emerg. Med. Clin. N. Am. 2016, 34, 883–899. [Google Scholar] [CrossRef]
- Palmer, C.; Menzies, S.L.; Roberts, R.L.; Pavlick, G.; Connor, J.R. Changes in Iron Histochemistry after Hypoxic-Ischemic Brain Injury in the Neonatal Rat. J. Neurosci. Res. 1999, 56, 60–71. [Google Scholar] [CrossRef]
- García-Yébenes, I.; Sobrado, M.; Moraga, A.; Zarruk, J.G.; Romera, V.G.; Pradillo, J.M.; de la Ossa, N.P.; Moro, M.A.; Dávalos, A.; Lizasoain, I. Iron Overload, Measured as Serum Ferritin, Increases Brain Damage Induced by Focal Ischemia and Early Reperfusion. Neurochem. Int. 2012, 61, 1364–1369. [Google Scholar] [CrossRef]
- Davalos, A.; Castillo, J.; Marrugat, J.; Fernandez-Real, J.M.; Armengou, A.; Cacabelos, P.; Rama, R. Body Iron Stores and Early Neurologic Deterioration in Acute Cerebral Infarction. Neurology 2000, 54, 1568–1574. [Google Scholar] [CrossRef] [PubMed]
- Mehta, S.H.; Webb, R.C.; Ergul, A.; Tawak, A.; Dorrance, A.M. Neuroprotection by Tempol in a Model of Iron-Induced Oxidative Stress in Acute Ischemic Stroke. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2004, 286, R283–R288. [Google Scholar] [CrossRef] [PubMed]
- Keep, R.F.; Hua, Y.; Xi, G. Intracerebral Haemorrhage: Mechanisms of Injury and Therapeutic Targets. Lancet. Neurol. 2012, 11, 720–731. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.; Wu, Y.; Yuan, S.; Zhang, P.; Zhang, J.; Li, H.; Li, X.; Shen, H.; Wang, Z.; Chen, G. Glutathione Peroxidase 4 Participates in Secondary Brain Injury through Mediating Ferroptosis in a Rat Model of Intracerebral Hemorrhage. Brain Res. 2018, 1701, 112–125. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Han, X.; Lan, X.; Gao, Y.; Wan, J.; Durham, F.; Cheng, T.; Yang, J.; Wang, Z.; Jiang, C.; et al. Inhibition of Neuronal Ferroptosis Protects Hemorrhagic Brain. JCI Insight 2017, 2, e90777. [Google Scholar] [CrossRef]
- Deng, X.-X.; Li, S.-S.; Sun, F.-Y. Necrostatin-1 Prevents Necroptosis in Brains after Ischemic Stroke Via Inhibition of Ripk1-Mediated Ripk3/Mlkl Signaling. Aging Dis. 2019, 10, 807–817. [Google Scholar] [CrossRef]
- Zhu, Y.-M.; Lin, L.; Wei, C.; Guo, Y.; Qin, Y.; Li, Z.-S.; Kent, T.A.; McCoy, C.E.; Wang, Z.-X.; Ni, Y.; et al. The Key Regulator of Necroptosis, Rip1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke. Transl. Stroke Res. 2021, 12, 991–1017. [Google Scholar] [CrossRef]
- Lule, S.; Wu, L.; Sarro-Schwartz, A.; Iii, W.J.E.; Izzy, S.; Songtachalert, T.; Ahn, S.H.; Fernandes, N.D.; Jin, G.; Chung, J.Y.; et al. Cell-Specific Activation of Ripk1 and Mlkl after Intracerebral Hemorrhage in Mice. J. Cereb. Blood Flow Metab. 2021, 41, 1623–1633. [Google Scholar] [CrossRef]
- Su, X.; Wang, H.; Kang, D.; Zhu, J.; Sun, Q.; Li, T.; Ding, K. Necrostatin-1 Ameliorates Intracerebral Hemorrhage-Induced Brain Injury in Mice through Inhibiting Rip1/Rip3 Pathway. Neurochem. Res. 2015, 40, 643–650. [Google Scholar] [CrossRef]
- Wang, K.; Sun, Z.; Ru, J.; Wang, S.; Huang, L.; Ruan, L.; Lin, X.; Jin, K.; Zhuge, Q.; Yang, S. Ablation of Gsdmd Improves Outcome of Ischemic Stroke through Blocking Canonical and Non-Canonical Inflammasomes Dependent Pyroptosis in Microglia. Front. Neurol. 2020, 11, 577927. [Google Scholar] [CrossRef]
- Xu, P.; Hong, Y.; Xie, Y.; Yuan, K.; Li, J.; Sun, R.; Zhang, X.; Shi, X.; Li, R.; Wu, J.; et al. Trem-1 Exacerbates Neuroinflammatory Injury via Nlrp3 Inflammasome-Mediated Pyroptosis in Experimental Subarachnoid Hemorrhage. Transl. Stroke Res. 2021, 12, 643–659. [Google Scholar] [CrossRef] [PubMed]
- Chen, A.Q.; Fang, Z.; Chen, X.L.; Yang, S.; Zhou, Y.F.; Mao, L.; Xia, Y.P.; Jin, H.J.; Li, Y.N.; You, M.F.; et al. Microglia-Derived Tnf-A Mediates Endothelial Necroptosis Aggravating Blood Brain-Barrier Disruption after Ischemic Stroke. Cell Death Dis. 2019, 10, 487. [Google Scholar] [CrossRef] [PubMed]
- Naito, M.G.; Xu, D.; Amin, P.; Lee, J.; Wang, H.; Li, W.; Kelliher, M.; Pasparakis, M.; Yuan, J. Sequential Activation of Necroptosis and Apoptosis Cooperates to Mediate Vascular and Neural Pathology in Stroke. Proc. Natl. Acad. Sci. USA 2020, 117, 4959–4970. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.-Y.; Liu, W.-N.; Li, Y.-Q.; Zhang, X.-J.; Yang, J.; Luo, X.-J.; Peng, J. Ligustroflavone Reduces Necroptosis in Rat Brain after Ischemic Stroke through Targeting Ripk1/Ripk3/Mlkl Pathway. Naunyn Schmiedebergs Arch. Pharmacol. 2019, 392, 1085–1095. [Google Scholar] [CrossRef]
- Shen, H.; Liu, C.; Zhang, D.; Yao, X.; Zhang, K.; Li, H.; Chen, G. Role for Rip1 in Mediating Necroptosis in Experimental Intracerebral Hemorrhage Model both in Vivo and in Vitro. Cell Death Dis. 2017, 8, e2641. [Google Scholar] [CrossRef]
- Yang, L.; Wang, Y.; Zhang, C.; Chen, T.; Cheng, H. Perampanel, an Ampar Antagonist, Alleviates Experimental Intracerebral Hemorrhage-Induced Brain Injury via Necroptosis and Neuroinflammation. Mol. Med. Rep. 2021, 24, 544. [Google Scholar] [CrossRef]
- Rabuffetti, M.; Sciorati, C.; Tarozzo, G.; Clementi, E.; Manfredi, A.A.; Beltramo, M. Inhibition of Caspase-1-Like Activity by Ac-Tyr-Val-Ala-Asp-Chloromethyl Ketone Induces Long-Lasting Neuroprotection in Cerebral Ischemia through Apoptosis Reduction and Decrease of Proinflammatory Cytokines. J. Neurosci. Off. J. Soc. Neurosci. 2000, 20, 4398–4404. [Google Scholar] [CrossRef]
- Ross, J.; Brough, D.; Gibson, R.M.; Loddick, S.A.; Rothwell, N.J. A Selective, Non-Peptide Caspase-1 Inhibitor, Vrt-018858, Markedly Reduces Brain Damage Induced by Transient Ischemia in the Rat. Neuropharmacology 2007, 53, 638–642. [Google Scholar] [CrossRef]
- Fann, D.Y.-W.; Lee, S.-Y.; Manzanero, S.; Chunduri, P.; Sobey, C.G.; Arumugam, T.V. Pathogenesis of Acute Stroke and the Role of Inflammasomes. Ageing Res. Rev. 2013, 12, 941–966. [Google Scholar] [CrossRef]
- Fann, D.Y.-W.; Lee, S.-Y.; Manzanero, S.; Tang, S.-C.; Gelderblom, M.; Chunduri, P.; Bernreuther, C.; Glatzel, M.; Cheng, Y.-L.; Thundyil, J.; et al. Intravenous Immunoglobulin Suppresses Nlrp1 and Nlrp3 Inflammasome-Mediated Neuronal Death in Ischemic Stroke. Cell Death Dis. 2013, 4, e790. [Google Scholar] [CrossRef]
- Chen, S.; Ma, Q.; Krafft, P.R.; Hu, Q.; Rolland, W.; Sherchan, P.; Zhang, J.; Tang, J.; Zhang, J.H. P2x7r/Cryopyrin Inflammasome Axis Inhibition Reduces Neuroinflammation after Sah. Neurobiol. Dis. 2013, 58, 296–307. [Google Scholar] [CrossRef] [PubMed]
- Ma, Q.; Chen, S.; Hu, Q.; Feng, H.; Zhang, J.H.; Tang, J. Nlrp3 Inflammasome Contributes to Inflammation after Intracerebral Hemorrhage. Ann. Neurol. 2014, 75, 209–219. [Google Scholar] [CrossRef] [PubMed]
- Feng, L.; Chen, Y.; Ding, R.; Fu, Z.; Yang, S.; Deng, X.; Zeng, J. P2x7r Blockade Prevents Nlrp3 Inflammasome Activation and Brain Injury in a Rat Model of Intracerebral Hemorrhage: Involvement of Peroxynitrite. J. Neuroinflamm. 2015, 12, 190. [Google Scholar] [CrossRef]
- Dong, Y.; Fan, C.; Hu, W.; Jiang, S.; Ma, Z.; Yan, X.; Deng, C.; Di, S.; Xin, Z.; Wu, G.; et al. Melatonin Attenuated Early Brain Injury Induced by Subarachnoid Hemorrhage via Regulating Nlrp3 Inflammasome and Apoptosis Signaling. J. Pineal Res. 2016, 60, 253–262. [Google Scholar] [CrossRef] [PubMed]
- Wu, B.; Ma, Q.; Khatibi, N.; Chen, W.; Sozen, T.; Cheng, O.; Tang, J. Ac-Yvad-Cmk Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1β in Intracerebral Hemorrhage Mouse Model. Transl. Stroke Res. 2010, 1, 57–64. [Google Scholar] [CrossRef]
- Lin, X.; Ye, H.; Siaw-Debrah, F.; Pan, S.; He, Z.; Ni, H.; Xu, Z.; Jin, K.; Zhuge, Q.; Huang, L. Ac-Yvad-Cmk Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage. BioMed Res. Int. 2018, 2018, 3706047. [Google Scholar] [CrossRef]
Cell Death | Morphological Features | Biochemical Features | Key Genes | Ref. |
---|---|---|---|---|
Ferroptosis | Intact cell membrane, normal nuclear morphology, atrophy of mitochondria, increased density of mitochondrial membrane, and reduced or disappeared density of mitochondrial cristae | Iron accumulation and lipid peroxidation | GPX4, SLC7A11, TFR1, Nrf2, NCOA4, ACSL4, FSP1 | [6,7] |
Necroptosis | Organelle swelling, loss of plasma membrane integrity, and the breakdown of cell membranes leads to the release of cell contents | RIPK1, RIPK3, MLKL phosphorylation and ubiquitination, and formation of necrotic complexes in the cytoplasm | RIPK1, RIPK3, MLKL | [8,9,10,11,12,13] |
Pyroptosis | Cell swelling and formation of pores in the plasma membrane | Inflammasome formation, caspase and gasdermin activation and the release of numerous pro-inflammatory factors | caspase-1, GSDMD | [14,15,16,17] |
Apoptosis | Nucleus fragmentation, plasma membrane blistering, cell contraction | The formation of apoptotic bodies | Caspase, Bcl-2, Bax, Fas | [18] |
Cell Death | Target/Compound | Model | Effect | Mechanism | Ref. |
---|---|---|---|---|---|
Ferroptosis | GSH | PD patients | Induction | Decreased GSH, resulting in the formation of toxic hydroxyl radicals and ROS. | [52] |
Deferiprone | PD patients | Inhibition | Using deferiprone to inhibit the accumulation of iron ions, the patient showed clinical and radiological improvement. | [53] | |
Ferritin | AD patients | Induction | Increased ferritin in AD brains induces ferroptosis by enhancing oxidative stress through the fenton response. | [54] | |
GSH | AD patients | Induction | Decreased GSH in hippocampus and frontal cortex is associated with decline in cognitive function. | [55] | |
GPX4 | Gpx4BIKO mice | Induction | Gpx4BIKO mice induce elevated lipid peroxidation leading to cognitive impairment and neurodegeneration. | [56] | |
iron | HD patients | Induction | Altered iron homeostasis in the brain maybe involved in Huntington’s disease pathophysiology. | [57] | |
Nrf2 | HD mice and HD patients | Inhibition | The selective Nrf2 inducer MIND4–17 inhibits the expression of proinflammatory cytokines in primary microglia and astrocytes. | [58] | |
Necroptosis | RIPK1 | PD mice | Induction | Necroptosis is involved in neurodegeneration of dopaminergic neurons through miR-425-mediated activation of RIPK1. | [59] |
Nec-1s | PD mice | Inhibition | Nec-1s inhibition of necroptosis effectively reduces DA neuron loss caused by MPTP-dependent mitochondrial intoxication. | [60] | |
RIPK1, RIPK3 and MLKL | PD patients and PD mice | Induction | Key components of necroptosis mechanisms are activated in the axons and soma of dopaminergic neurons of SNpc in the PD model. | [61] | |
granulovacuolar degeneration | AD patients | Induction | The presence of activated necrosome complexes in granulovacuolar degeneration and its association with neuronal loss. | [62] | |
O-GlcNAcylation | AD patients and AD mice | Inhibition | O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) ameliorates model neuronal death and cognitive dysfunction by inhibiting necroptosis. | [63] | |
TNF/TNFR1 | AD patients | Induction | TNF/TNFR1 mediates necroptosis in AD patients, resulting in neuronal loss. | [64] | |
Nec-1 | APP/PS1 double-transgenic mice | Inhibition | Nec-1 directly targets Aβ and tau proteins, attenuates brain cell death and improves cognitive impairment in AD models. | [65] | |
Nec-1 | R6/2 transgenic mice | Inhibition | Nec-1 suppresses necroptosis in R6/2 transgenic mice, thereby improving HD symptoms. | [66] | |
Pyroptosis | miR-7 | PD patients and PD mice | Inhibition | Transfection of miR-7 inhibited the activation of the NLRP3 inflammasome in microglial cells, accompanied by an inhibition of caspase-1 activation and reduced IL-1β production. | [67] |
α-synuclein | PD patients | Induction | IL-1β, NLRP3 levels were significantly increased in PD. We also observed a linear correlation of NLRP3 with α-synuclein. | [68] | |
Aβ | APP/PS1 double-transgenic mice | Induction | Aβ aggregates can activate the NLRP3 inflammatory pathway, and NLRP3 promotes the maturation of caspase-1. | [69] | |
Aβ | APP/PS1 double-transgenic mice | Induction | Aβ regulates pyroptosis through NLRP3-caspase-1 signaling. | [70] | |
GSDMD | AD patients | Induction | The increased expression of GSDMD in the cerebrospinal fluid of AD patients has certain diagnostic value for AD. | [71] | |
NLRP3 | R6/2 transgenic mice | Induction | NLRP3-mediated pyroptosis leads to degeneration of HD neurons. | [72] | |
MCC950 | R6/2 transgenic mice | Inhibition | MCC950 delays HD disease progression by inhibiting NLRP3. | [73] |
Cell Death | Target/Compound | Model | Effect | Mechanism | Ref. |
---|---|---|---|---|---|
Ferroptosis | fer-1 | TBI mice | Inhibition | Fer-1 treatment reduces neuronal cell death and improves long-term cognitive and motor function. | [109] |
EAAC1 | TBI male mice from EAAC1 −/− colony | Induction | EAAC1 −/− mice promoted increased ROS and neuronal damage after TBI model by inhibiting cysteine uptake. | [113] | |
Necroptosis | CHMP4B | TBI mice | Inhibition | CHMP4B improves motor and memory function in TBI model mice by alleviating necroptosis of microglia. | [114] |
RIPK1, RIPK3 | TBI mice | Induction | Ripk3 global knockout animals, as well as neuronal RIPK1-deficient mice, were protected from chronic brain injury by inhibiting downstream pMLKL and improved neurocognitive function after TBI. | [115] | |
RIPK3 | TBI mice | Induction | RIPK3 was highly induced after TBI, and RIPK3 knockout reduced inflammation by inactivating the NLRP3 and NF-κB pathways, and attenuated brain injury after TBI. | [116] | |
Pyroptosis | AC-FLTD-CMK | TBI mice | Inhibition | AC-FLTD-CMK administration reduced a key protein of necroptosis in a TBI model, and attenuated neuronal damage and brain edema. | [117] |
VX765 | TBI mice | Inhibition | VX765 provides neuroprotection in TBI model mice by inhibiting caspase-1. | [118] | |
MCC950 | TBI mice | Inhibition | MCC950 attenuated pyroptosis-induced inflammatory damage by inhibiting NLRP3 and significantly improved neurological function in TBI mice. | [119] |
Cell Death | Target/Compound | Model | Effect | Mechanism | Ref. |
---|---|---|---|---|---|
Ferroptosis | iron | MCAO mice | Induction | Iron overload leads to increased brain edema and hemorrhage area in mice with cerebral ischemia through fenton translation. | [130] |
tempol | MCAO mice | Inhibition | In mice model of MCAO, tempol reversed the size of the infarct size increased by iron treatment. | [132] | |
fer-1 | ICH mice | Inhibition | The use of Fer-1 in ICH model mice can reduce neuronal death and improve neural function by inhibiting lipid ROS. | [135] | |
GPX4 | ICH rats | Inhibition | Overexpression of GPX4 ameliorated secondary brain injury after ICH by inhibiting ferroptosis. | [134] | |
Necroptosis | Nec-1 | MCAO rats | Inhibition | Nec-1 inhibits necroptosis by inhibiting RIPK1 phosphorylation in rat model of MCAO. | [136] |
RIPK1 | MCAO rats | Induction | A key regulator of necroptosis, RIPK1, is involved in astrogliosis and glial scar formation. | [137] | |
RIPK1 | ICH mice | Induction | RIPK1 leads to increased blood-brain barrier permeability and brain edema in ICH model mice through MLKL-mediated necroptosis. | [138] | |
Nec-1 | ICH mice | Inhibition | Nec-1 improves neurobehavioral ability and brain edema by inhibiting RIPK1/RIPK3 pathway after ICH in mice. | [139] | |
Pyroptosis | GSDMD | MCAO mice | Induction | GSDMD-induced pyroptosis leads to neurological deficits and abundant neuronal cell death in MCAO mice. | [140] |
TREM-1 | SAH mice | Induction | TREM-1 exacerbates neuroinflammation through NLRP3 inflammasome-mediated pyroptosis after SAH. | [141] |
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Tang, L.; Liu, S.; Li, S.; Chen, Y.; Xie, B.; Zhou, J. Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis: A Novel Therapeutic Target in Nervous System Diseases. Int. J. Mol. Sci. 2023, 24, 10127. https://doi.org/10.3390/ijms241210127
Tang L, Liu S, Li S, Chen Y, Xie B, Zhou J. Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis: A Novel Therapeutic Target in Nervous System Diseases. International Journal of Molecular Sciences. 2023; 24(12):10127. https://doi.org/10.3390/ijms241210127
Chicago/Turabian StyleTang, Lu, Sitong Liu, Shiwei Li, Ye Chen, Bingqing Xie, and Jun Zhou. 2023. "Induction Mechanism of Ferroptosis, Necroptosis, and Pyroptosis: A Novel Therapeutic Target in Nervous System Diseases" International Journal of Molecular Sciences 24, no. 12: 10127. https://doi.org/10.3390/ijms241210127