Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies
Abstract
:1. Introduction
2. Mechanisms of Cell Death Involved in DN
2.1. Oxidative Stress
2.2. Mitochondrial Dysfunction
2.3. Inflammation
2.4. ER Stress
2.5. Glutamate-Induced Excitotoxicity
3. Types of Cell Death and Potential Targets in DN
3.1. Apoptosis in DN
3.2. Autophagy
3.3. Necrosis in DN
3.3.1. Pyroptosis
3.3.2. Necroptosis
3.4. Other Types of Cell Death
3.4.1. Ferroptosis
3.4.2. Parthanatos
4. Future Perspectives
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Feldman, E.L.; Callaghan, B.C.; Pop-Busui, R.; Zochodne, D.W.; Wright, D.E.; Bennett, D.L.; Bril, V.; Russell, J.W.; Viswanathan, V. Diabetic Neuropathy. Nat. Rev. Dis. Primers 2019, 5, 41. [Google Scholar] [CrossRef] [PubMed]
- Dyck, P.J.; Kratz, K.M.; Karnes, J.L.; Litchy, W.J.; Klein, R.; Pach, J.M.; Wilson, D.M.; O’Brien, P.C.; Melton, L.J. The Prevalence by Staged Severity of Various Types of Diabetic Neuropathy, Retinopathy, and Nephropathy in a Population-Based Cohort: The Rochester Diabetic Neuropathy Study. Neurology 1993, 43, 817. [Google Scholar] [CrossRef] [PubMed]
- Pop-Busui, R.; Boulton, A.J.M.; Feldman, E.L.; Bril, V.; Freeman, R.; Malik, R.A.; Sosenko, J.M.; Ziegler, D. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care 2017, 40, 136–154. [Google Scholar] [CrossRef] [PubMed]
- Tesfaye, S.; Boulton, A.J.M.; Dyck, P.J.; Freeman, R.; Horowitz, M.; Kempler, P.; Lauria, G.; Malik, R.A.; Spallone, V.; Vinik, A.; et al. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care 2010, 33, 2285–2293. [Google Scholar] [CrossRef] [PubMed]
- Galer, B.S.; Gianas, A.; Jensen, M.P. Painful Diabetic Polyneuropathy: Epidemiology, Pain Description, and Quality of Life. Diabetes Res. Clin. Pract. 2000, 47, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Moheet, A.; Mangia, S.; Seaquist, E.R. Impact of Diabetes on Cognitive Function and Brain Structure. Ann. N. Y. Acad. Sci. 2015, 1353, 60–71. [Google Scholar] [CrossRef] [PubMed]
- Martins, I.; Raza, S.Q.; Voisin, L.; Dakhli, H.; Law, F.; De Jong, D.; Allouch, A.; Thoreau, M.; Brenner, C.; Deutsch, E.; et al. Entosis: The Emerging Face of Non-Cell-Autonomous Type IV Programmed Death. Biomed. J. 2017, 40, 133–140. [Google Scholar] [CrossRef] [PubMed]
- Chaudhary, P.; Janmeda, P.; Docea, A.O.; Yeskaliyeva, B.; Abdull Razis, A.F.; Modu, B.; Calina, D.; Sharifi-Rad, J. Oxidative Stress, Free Radicals and Antioxidants: Potential Crosstalk in the Pathophysiology of Human Diseases. Front. Chem. 2023, 11, 1158198. [Google Scholar] [CrossRef] [PubMed]
- Mizukami, H.; Osonoi, S. Collateral Glucose-Utlizing Pathwaya in Diabetic Polyneuropathy. Int. J. Mol. Sci. 2021, 22, 94. [Google Scholar] [CrossRef] [PubMed]
- Ighodaro, O.M. Molecular Pathways Associated with Oxidative Stress in Diabetes Mellitus. Biomed. Pharmacother. 2018, 108, 656–662. [Google Scholar] [CrossRef] [PubMed]
- Papachristoforou, E.; Lambadiari, V.; Maratou, E.; Makrilakis, K. Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications. J. Diabetes Res. 2020, 2020, 7489795. [Google Scholar] [CrossRef] [PubMed]
- Figueroa-Romero, C.; Sadidi, M.; Feldman, E.L. Mechanisms of Disease: The Oxidative Stress Theory of Diabetic Neuropathy. Rev. Endocr. Metab. Disord. 2008, 9, 301–314. [Google Scholar] [CrossRef] [PubMed]
- Feldman, E.L.; Nave, K.-A.; Jensen, T.S.; Bennett, D.L.H. New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain. Neuron 2017, 93, 1296–1313. [Google Scholar] [CrossRef] [PubMed]
- Luna, R.; Talanki Manjunatha, R.; Bollu, B.; Jhaveri, S.; Avanthika, C.; Reddy, N.; Saha, T.; Gandhi, F. A Comprehensive Review of Neuronal Changes in Diabetics. Cureus 2021, 13, e19142. [Google Scholar] [CrossRef] [PubMed]
- Sourris, K.C.; Watson, A.; Jandeleit-Dahm, K. Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation. In Reactive Oxygen Species; Schmidt, H.H.H.W., Ghezzi, P., Cuadrado, A., Eds.; Handbook of Experimental Pharmacology; Springer International Publishing: Cham, Switzerland, 2020; Volume 264, pp. 395–423. ISBN 978-3-030-68509-6. [Google Scholar]
- Oshitari, T. Neurovascular Impairment and Therapeutic Strategies in Diabetic Retinopathy. Int. J. Environ. Res. Public Health 2022, 19, 439. [Google Scholar] [CrossRef] [PubMed]
- Lai, M.C.; Liu, W.Y.; Liou, S.-S.; Liu, I.-M. The Protective Effects of Moscatilin against Methylglyoxal-Induced Neurotoxicity via the Regulation of P38/JNK MAPK Pathways in PC12 Neuron-like Cells. Food Chem. Toxicol. 2020, 140, 111369. [Google Scholar] [CrossRef] [PubMed]
- Pang, L.; Lian, X.; Liu, H.; Zhang, Y.; Li, Q.; Cai, Y.; Ma, H.; Yu, X. Understanding Diabetic Neuropathy: Focus on Oxidative Stress. Oxid. Med. Cell. Longev. 2020, 2020, e9524635. [Google Scholar] [CrossRef] [PubMed]
- Nakajima, H.; Kubo, T.; Ihara, H.; Hikida, T.; Danjo, T.; Nakatsuji, M.; Shahani, N.; Itakura, M.; Ono, Y.; Azuma, Y.-T.; et al. Nuclear-Translocated Glyceraldehyde-3-Phosphate Dehydrogenase Promotes Poly(ADP-Ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke. J. Biol. Chem. 2015, 290, 14493–14503. [Google Scholar] [CrossRef] [PubMed]
- Virág, L.; Robaszkiewicz, A.; Rodriguez-Vargas, J.M.; Oliver, F.J. Poly(ADP-Ribose) Signaling in Cell Death. Mol. Asp. Med. 2013, 34, 1153–1167. [Google Scholar] [CrossRef] [PubMed]
- Montgomery, M.K.; Turner, N. Mitochondrial Dysfunction and Insulin Resistance: An Update. Endocr. Connect. 2015, 4, R1–R15. [Google Scholar] [CrossRef] [PubMed]
- Russell, J.W.; Golovoy, D.; Vincent, A.M.; Mahendru, P.; Olzmann, J.A.; Mentzer, A.; Feldman, E.L. High Glucose-induced Oxidative Stress and Mitochondrial Dysfunction in Neurons. FASEB J. 2002, 16, 1738–1748. [Google Scholar] [CrossRef] [PubMed]
- Román-Pintos, L.M.; Villegas-Rivera, G.; Rodríguez-Carrizalez, A.D.; Miranda-Díaz, A.G.; Cardona-Muñoz, E.G. Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function. J. Diabetes Res. 2016, 2016, 3425617. [Google Scholar] [CrossRef] [PubMed]
- Srinivasan, S.; Stevens, M.; Wiley, J.W. Diabetic Peripheral Neuropathy: Evidence for Apoptosis and Associated Mitochondrial Dysfunction. Diabetes 2000, 49, 1932–1938. [Google Scholar] [CrossRef] [PubMed]
- Feng, B.; Ruiz, M.A.; Chakrabarti, S. Oxidative-Stress-Induced Epigenetic Changes in Chronic Diabetic Complications. Can. J. Physiol. Pharmacol. 2013, 91, 213–220. [Google Scholar] [CrossRef] [PubMed]
- Baum, P.; Toyka, K.V.; Blüher, M.; Kosacka, J.; Nowicki, M. Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)—New Aspects. Int. J. Mol. Sci. 2021, 22, 10835. [Google Scholar] [CrossRef] [PubMed]
- Vincent, A.M.; Calabek, B.; Roberts, L.; Feldman, E.L. Biology of Diabetic Neuropathy. Handb. Clin. Neurol. 2013, 115, 591–606. [Google Scholar] [CrossRef] [PubMed]
- Schwarz, D.S.; Blower, M.D. The Endoplasmic Reticulum: Structure, Function and Response to Cellular Signaling. Cell. Mol. Life Sci. 2016, 73, 79–94. [Google Scholar] [CrossRef] [PubMed]
- Hetz, C. The Unfolded Protein Response: Controlling Cell Fate Decisions under ER Stress and Beyond. Nat. Rev. Mol. Cell Biol. 2012, 13, 89–102. [Google Scholar] [CrossRef] [PubMed]
- Almanza, A.; Carlesso, A.; Chintha, C.; Creedican, S.; Doultsinos, D.; Leuzzi, B.; Luís, A.; McCarthy, N.; Montibeller, L.; More, S.; et al. Endoplasmic Reticulum Stress Signalling—From Basic Mechanisms to Clinical Applications. FEBS J. 2019, 286, 241–278. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.-H.; Lee, J. Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β-Cell Dysfunction and Senescence in Type 2 Diabetes. Int. J. Mol. Sci. 2022, 23, 4843. [Google Scholar] [CrossRef]
- Yang, H.; Niemeijer, M.; van de Water, B.; Beltman, J.B. ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response. iScience 2020, 23, 100860. [Google Scholar] [CrossRef] [PubMed]
- Sano, R.; Reed, J.C. ER Stress-Induced Cell Death Mechanisms. Biochim. Biophys. Acta-Mol. Cell Res. 2013, 1833, 3460–3470. [Google Scholar] [CrossRef] [PubMed]
- Hetz, C.; Papa, F.R. The Unfolded Protein Response and Cell Fate Control. Mol. Cell 2018, 69, 169–181. [Google Scholar] [CrossRef] [PubMed]
- Han, J.; Back, S.H.; Hur, J.; Lin, Y.-H.; Gildersleeve, R.; Shan, J.; Yuan, C.L.; Krokowski, D.; Wang, S.; Hatzoglou, M.; et al. ER-Stress-Induced Transcriptional Regulation Increases Protein Synthesis Leading to Cell Death. Nat. Cell Biol. 2013, 15, 481–490. [Google Scholar] [CrossRef] [PubMed]
- Yang, D.; Xie, J.; Liang, X.-C.; Cui, Y.-Z.; Wu, Q.-L. The Synergistic Effect of Palmitic Acid and Glucose on Inducing Endoplasmic Reticulum Stress-Associated Apoptosis in Rat Schwann Cells. Eur. Rev. Med. Pharmacol. Sci. 2022, 26, 148–157. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.-B.; Li, H.-Q.; Ren, M.-S.; Li, W.-T.; Lv, X.-Y.; Wang, L. CHOP/ORP150 Ratio in Endoplasmic Reticulum Stress: A New Mechanism for Diabetic Peripheral Neuropathy. Cell Physiol. Biochem. 2013, 32, 367–379. [Google Scholar] [CrossRef] [PubMed]
- Maragakis, N.J.; Rothstein, J.D. Glutamate Transporters in Neurologic Disease. Arch. Neurol. 2001, 58, 365–370. [Google Scholar] [CrossRef] [PubMed]
- Gasic, G.P.; Hollmann, M. Molecular Neurobiology of Glutamate Receptors. Annu. Rev. Physiol. 1992, 54, 507–536. [Google Scholar] [CrossRef] [PubMed]
- Shen, Z.; Xiang, M.; Chen, C.; Ding, F.; Wang, Y.; Shang, C.; Xin, L.; Zhang, Y.; Cui, X. Glutamate Excitotoxicity: Potential Therapeutic Target for Ischemic Stroke. Biomed. Pharmacother. 2022, 151, 113125. [Google Scholar] [CrossRef] [PubMed]
- Yu, S.P.; Jiang, M.Q.; Shim, S.S.; Pourkhodadad, S.; Wei, L. Extrasynaptic NMDA Receptors in Acute and Chronic Excitotoxicity: Implications for Preventive Treatments of Ischemic Stroke and Late-Onset Alzheimer’s Disease. Mol. Neurodegener. 2023, 18, 43. [Google Scholar] [CrossRef] [PubMed]
- Jayanarayanan, S.; Smijin, S.; Peeyush, K.T.; Anju, T.R.; Paulose, C.S. NMDA and AMPA Receptor Mediated Excitotoxicity in Cerebral Cortex of Streptozotocin Induced Diabetic Rat: Ameliorating Effects of Curcumin. Chem.-Biol. Interact. 2013, 201, 39–48. [Google Scholar] [CrossRef] [PubMed]
- Ketelut-Carneiro, N.; Fitzgerald, K.A. Apoptosis, Pyroptosis, and Necroptosis—Oh My! The Many Ways a Cell Can Die. J. Mol. Biol. 2022, 434, 167378. [Google Scholar] [CrossRef] [PubMed]
- Green, D.R.; Llambi, F. Cell Death Signaling. Cold Spring Harb. Perspect. Biol. 2015, 7, a006080. [Google Scholar] [CrossRef] [PubMed]
- D’Arcy, M.S. Cell Death: A Review of the Major Forms of Apoptosis, Necrosis and Autophagy. Cell Biol. Int. 2019, 43, 582–592. [Google Scholar] [CrossRef] [PubMed]
- Russell, J.W.; Sullivan, K.A.; Windebank, A.J.; Herrmann, D.N.; Feldman, E.L. Neurons Undergo Apoptosis in Animal and Cell Culture Models of Diabetes. Neurobiol. Dis. 1999, 6, 347–363. [Google Scholar] [CrossRef] [PubMed]
- Jessen, K.R.; Mirsky, R. The Repair Schwann Cell and Its Function in Regenerating Nerves. J. Physiol. 2016, 594, 3521–3531. [Google Scholar] [CrossRef] [PubMed]
- Rosenberger, D.C.; Blechschmidt, V.; Timmerman, H.; Wolff, A.; Treede, R.-D. Challenges of Neuropathic Pain: Focus on Diabetic Neuropathy. J. Neural Transm. 2020, 127, 589–624. [Google Scholar] [CrossRef] [PubMed]
- Jiang, Z.; Bian, M.; Wu, J.; Li, D.; Ding, L.; Zeng, Q. Oltipraz Prevents High Glucose-Induced Oxidative Stress and Apoptosis in RSC96 Cells through the Nrf2/NQO1 Signalling Pathway. BioMed Res. Int. 2020, 2020, 5939815. [Google Scholar] [CrossRef] [PubMed]
- Li, K.; Shi, X.; Luo, M.; Inam-U-Llah; Wu, P.; Zhang, M.; Zhang, C.; Li, Q.; Wang, Y.; Piao, F. Taurine Protects against Myelin Damage of Sciatic Nerve in Diabetic Peripheral Neuropathy Rats by Controlling Apoptosis of Schwann Cells via NGF/Akt/GSK3β Pathway. Exp. Cell Res. 2019, 383, 111557. [Google Scholar] [CrossRef] [PubMed]
- Mizisin, A.P. Mechanisms of Diabetic Neuropathy. In Handbook of Clinical Neurology; Elsevier: Amsterdam, The Netherlands, 2014; Volume 126, pp. 401–428. [Google Scholar] [CrossRef]
- Ren, G.; Kong, J.; Jia, N.; Shang, X. Luteolin Attenuates Neuronal Apoptosis in the Hippocampi of Diabetic Encephalopathy Rats. Neural Regen. Res. 2013, 8, 1071–1080. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Liu, G.; He, F.; Zhang, L.; Yang, K.; Yu, H.; Zhou, J.; Gan, H. MicroRNA 375 Modulates Hyperglycemia-Induced Enteric Glial Cell Apoptosis and Diabetes-Induced Gastrointestinal Dysfunction by Targeting Pdk1 and Repressing PI3K/Akt Pathway. Sci. Rep. 2018, 8, 12681. [Google Scholar] [CrossRef] [PubMed]
- Maione, S.; Siniscalco, D.; Galderisi, U.; De Novellis, V.; Uliano, R.; Di Bernardo, G.; Berrino, L.; Cascino, A.; Rossi, F. Apoptotic Genes Expression in the Lumbar Dorsal Horn in a Model Neuropathic Pain in Rat. NeuroReport 2002, 13, 101–106. [Google Scholar] [CrossRef] [PubMed]
- De Novellis, V.; Siniscalco, D.; Galderisi, U.; Fuccio, C.; Nolano, M.; Santoro, L.; Cascino, A.; Roth, K.A.; Rossi, F.; Maione, S. Blockade of Glutamate mGlu5 Receptors in a Rat Model of Neuropathic Pain Prevents Early Over-Expression of pro-Apoptotic Genes and Morphological Changes in Dorsal Horn Lamina II. Neuropharmacology 2004, 46, 468–479. [Google Scholar] [CrossRef] [PubMed]
- Kaeidi, A.; Esmaeili-Mahani, S.; Abbasnejad, M.; Sheibani, V.; Rasoulian, B.; Hajializadeh, Z.; Pasban-Aliabadi, H. Satureja Khuzestanica Attenuates Apoptosis in Hyperglycemic PC12 Cells and Spinal Cord of Diabetic Rats. J. Nat. Med. 2013, 67, 61–69. [Google Scholar] [CrossRef] [PubMed]
- Elsayed, H.R.H.; Ali, E.M.T.; Rabei, M.R.; El Nashar, E.M.; Alghamdi, M.A.; Al-Zahrani, N.S.; Alshehri, S.H.; Aldahhan, R.A.; Morsy, A.I. Angiotensin II Type 1 Receptor Blockade Attenuates the Neuropathological Changes in the Spinal Cords of Diabetic Rats with Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase 1 System. Tissue Cell 2024, 88, 102420. [Google Scholar] [CrossRef] [PubMed]
- Oyenihi, A.B.; Ayeleso, A.O.; Mukwevho, E.; Masola, B. Antioxidant Strategies in the Management of Diabetic Neuropathy. BioMed Res. Int. 2015, 2015, e515042. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Zhang, D.; Zhang, Z.; Tian, J.; An, J.; Zhang, W.; Ben, Y. Alpha-Lipoic Acid Activates AMPK to Protect against Oxidative Stress and Apoptosis in Rats with Diabetic Peripheral Neuropathy. Hormones 2023, 22, 95–105. [Google Scholar] [CrossRef] [PubMed]
- Sadeghiyan Galeshkalami, N.; Abdollahi, M.; Najafi, R.; Baeeri, M.; Jamshidzade, A.; Falak, R.; Davoodzadeh Gholami, M.; Hassanzadeh, G.; Mokhtari, T.; Hassani, S.; et al. Alpha-Lipoic Acid and Coenzyme Q10 Combination Ameliorates Experimental Diabetic Neuropathy by Modulating Oxidative Stress and Apoptosis. Life Sci. 2019, 216, 101–110. [Google Scholar] [CrossRef] [PubMed]
- Tasci, I.; Demir, C.F.; Kuloglu, T. Effects of Alpha Lipoic Acid on Loss of Myelin Sheath of Sciatic Nerve in Experimentally Induced Diabetic Rats. Med. Arch. 2018, 72, 178–181. [Google Scholar] [CrossRef] [PubMed]
- Papanas, N.; Ziegler, D. Efficacy of α-Lipoic Acid in Diabetic Neuropathy. Expert Opin. Pharmacother. 2014, 15, 2721–2731. [Google Scholar] [CrossRef] [PubMed]
- Baicus, C.; Purcarea, A.; von Elm, E.; Delcea, C.; Furtunescu, F.L. Alpha-lipoic Acid for Diabetic Peripheral Neuropathy. Cochrane Database Syst. Rev. 2024, 1, CD012967. [Google Scholar] [CrossRef]
- Xu, S.; Bao, W.; Men, X.; Liu, Y.; Sun, J.; Li, J.; Liu, H.; Cai, H.; Zhang, W.; Lou, J.; et al. Interleukin-10 Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis via NF-κB Suppression. Exp. Clin. Endocrinol. Diabetes 2020, 128, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Xu, S.; Li, J.; Zhai, M.; Yao, X.; Liu, H.; Deng, T.; Cai, H.; Zhang, W.; Zhang, W.; Lou, J.; et al. 1,25-(OH)(2)D(3) Protects Schwann Cells against Advanced Glycation End Products-Induced Apoptosis through PKA-NF-κB Pathway. Life Sci. 2019, 225, 107–116. [Google Scholar] [CrossRef] [PubMed]
- Chen, L.; Chen, Z.; Xu, Z.; Feng, W.; Yang, X.; Qi, Z. Polydatin Protects Schwann Cells from Methylglyoxal Induced Cytotoxicity and Promotes Crushed Sciatic Nerves Regeneration of Diabetic Rats. Phytother. Res. PTR 2021, 35, 4592–4604. [Google Scholar] [CrossRef] [PubMed]
- Kalamkar, S.; Acharya, J.; Kolappurath Madathil, A.; Gajjar, V.; Divate, U.; Karandikar-Iyer, S.; Goel, P.; Ghaskadbi, S. Randomized Clinical Trial of How Long-Term Glutathione Supplementation Offers Protection from Oxidative Damage and Improves HbA1c in Elderly Type 2 Diabetic Patients. Antioxidants 2022, 11, 1026. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.-J.; Zhang, T.-N.; Chen, H.-H.; Yu, X.-F.; Lv, J.-L.; Liu, Y.-Y.; Liu, Y.-S.; Zheng, G.; Zhao, J.-Q.; Wei, Y.-F.; et al. The Sirtuin Family in Health and Disease. Signal Transduct. Target. Ther. 2022, 7, 402. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Wei, Y.; Wei, Y.; Yu, H.; Zhang, W.; Li, C.; He, Y.; Yao, G.; Zhang, Y. Dexmedetomidine Alleviates Oxidative Stress and Mitochondrial Dysfunction in Diabetic Peripheral Neuropathy via the microRNA-34a/SIRT2/S1PR1 Axis. Int. Immunopharmacol. 2023, 117, 109910. [Google Scholar] [CrossRef] [PubMed]
- Jiang, W.; Hu, T.; Ye, C.; Hu, M.; Yu, Q.; Sun, L.; Liang, J.; Chen, Y. Formononetin Attenuates High Glucose-Induced Neurotoxicity by Negatively Regulating Oxidative Stress and Mitochondrial Dysfunction in Schwann Cells via Activation of SIRT3. Food Chem. Toxicol. 2023, 182, 114156. [Google Scholar] [CrossRef] [PubMed]
- Yao, Y.; Shi, J.; Zhang, C.; Gao, W.; Huang, N.; Liu, Y.; Yan, W.; Han, Y.; Zhou, W.; Kong, L. Pyruvate Dehydrogenase Kinase 1 Protects against Neuronal Injury and Memory Loss in Mouse Models of Diabetes. Cell Death Dis. 2023, 14, 722. [Google Scholar] [CrossRef] [PubMed]
- Gundu, C.; Arruri, V.K.; Sherkhane, B.; Khatri, D.K.; Singh, S.B. GSK2606414 Attenuates PERK/p-eIF2α/ATF4/CHOP Axis and Augments Mitochondrial Function to Mitigate High Glucose Induced Neurotoxicity in N2A Cells. Curr. Res. Pharmacol. Drug Discov. 2022, 3, 100087. [Google Scholar] [CrossRef] [PubMed]
- Gundu, C.; Arruri, V.K.; Sherkhane, B.; Khatri, D.K.; Singh, S.B. Indole-3-Propionic Acid Attenuates High Glucose Induced ER Stress Response and Augments Mitochondrial Function by Modulating PERK-IRE1-ATF4-CHOP Signalling in Experimental Diabetic Neuropathy. Arch. Physiol. Biochem. 2022, 130, 243–256. [Google Scholar] [CrossRef] [PubMed]
- Yao, W.; Yang, X.; Zhu, J.; Gao, B.; Shi, H.; Xu, L. IRE1α siRNA Relieves Endoplasmic Reticulum Stress-Induced Apoptosis and Alleviates Diabetic Peripheral Neuropathy In Vivo and In Vitro. Sci. Rep. 2018, 8, 2579. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.; Zhang, C.; Wang, C.; Huang, Y.; Liu, J.; Chu, H.; Ren, X.; Kong, L.; Ma, H. Thioredoxin-1 Is a Target to Attenuate Alzheimer-Like Pathology in Diabetic Encephalopathy by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress. Front. Physiol. 2021, 12, 651105. [Google Scholar] [CrossRef] [PubMed]
- Yao, W.; Yang, X.; Zhu, J.; Gao, B.; Liu, R.; Xu, L. Tang-Luo-Ning, a Traditional Chinese Medicine, Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis of Schwann Cells under High Glucose Environment. Evid. Based Complement. Altern. Med. 2017, 2017, 5193548. [Google Scholar] [CrossRef] [PubMed]
- Hu, Y.; Chen, C.; Liang, Z.; Liu, T.; Hu, X.; Wang, G.; Hu, J.; Xie, X.; Liu, Z. Compound Qiying Granules Alleviates Diabetic Peripheral Neuropathy by Inhibiting Endoplasmic Reticulum Stress and Apoptosis. Mol. Med. 2023, 29, 98. [Google Scholar] [CrossRef] [PubMed]
- Pivari, F.; Mingione, A.; Brasacchio, C.; Soldati, L. Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment. Nutrients 2019, 11, 1837. [Google Scholar] [CrossRef] [PubMed]
- Wu, T.; Li, X.; Tu, S.; Tan, W.; Chen, L. Curcumin Protect Schwann Cells from Inflammation Response and Apoptosis Induced by High Glucose through the NF-κB Pathway. Tissue Cell 2022, 77, 101873. [Google Scholar] [CrossRef] [PubMed]
- Elsayed, H.R.H.; Rabei, M.R.; Elshaer, M.M.A.; El Nashar, E.M.; Alghamdi, M.A.; Al-Qahtani, Z.; Nabawy, A. Suppression of Neuronal Apoptosis and Glial Activation with Modulation of Nrf2/HO-1 and NF-kB Signaling by Curcumin in Streptozotocin-Induced Diabetic Spinal Cord Central Neuropathy. Front. Neuroanat. 2023, 17, 1094301. [Google Scholar] [CrossRef] [PubMed]
- Zhang, W.-X.; Lin, Z.-Q.; Sun, A.-L.; Shi, Y.-Y.; Hong, Q.-X.; Zhao, G.-F. Curcumin Ameliorates the Experimental Diabetic Peripheral Neuropathy through Promotion of NGF Expression in Rats. Chem. Biodivers. 2022, 19, e202200029. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.-R.; Samoriski, G.; Pan, H.-L. Antinociceptive Effects of Chronic Administration of Uncompetitive NMDA Receptor Antagonists in a Rat Model of Diabetic Neuropathic Pain. Neuropharmacology 2009, 57, 121–126. [Google Scholar] [CrossRef] [PubMed]
- Aiyer, R.; Mehta, N.; Gungor, S.; Gulati, A. A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice. Clin. J. Pain. 2018, 34, 450–467. [Google Scholar] [CrossRef] [PubMed]
- Afrazi, S.; Esmaeili-Mahani, S.; Sheibani, V.; Abbasnejad, M. Neurosteroid Allopregnanolone Attenuates High Glucose-Induced Apoptosis and Prevents Experimental Diabetic Neuropathic Pain: In Vitro and in Vivo Studies. J. Steroid Biochem. Mol. Biol. 2014, 139, 98–103. [Google Scholar] [CrossRef] [PubMed]
- Mizushima, N.; Komatsu, M. Autophagy: Renovation of Cells and Tissues. Cell 2011, 147, 728–741. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; He, S.; Ma, B. Autophagy and Autophagy-Related Proteins in Cancer. Mol. Cancer 2020, 19, 12. [Google Scholar] [CrossRef] [PubMed]
- Medras, Z.J.H.; Mostafa, Y.M.; Ahmed, A.A.M.; El-Sayed, N.M. Arctigenin Improves Neuropathy via Ameliorating Apoptosis and Modulating Autophagy in Streptozotocin-Induced Diabetic Mice. CNS Neurosci. Ther. 2023, 29, 3068–3080. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez, C.D.; Lee, M.-S.; Marchetti, P.; Pietropaolo, M.; Towns, R.; Vaccaro, M.I.; Watada, H.; Wiley, J.W. The Emerging Role of Autophagy in the Pathophysiology of Diabetes Mellitus. Autophagy 2011, 7, 2–11. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Yao, S.; Yang, H.; Liu, S.; Wang, Y. Autophagy: Regulator of Cell Death. Cell Death Dis. 2023, 14, 648. [Google Scholar] [CrossRef] [PubMed]
- Zhou, W.; Yao, Y.; Li, J.; Wu, D.; Zhao, M.; Yan, Z.; Pang, A.; Kong, L. TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway. Front. Mol. Neurosci. 2019, 12, 193. [Google Scholar] [CrossRef] [PubMed]
- Nazarnezhad, S.; Rahmati, M.; Shayannia, A.; Abbasi, Z.; Salehi, M.; Khaksari, M. Nesfatin-1 Protects PC12 Cells against High Glucose-Induced Cytotoxicity via Inhibiting Oxidative Stress, Autophagy and Apoptosis. Neurotoxicology 2019, 74, 196–202. [Google Scholar] [CrossRef]
- Wang, Q.-Q.; Zhai, C.; Wahafu, A.; Zhu, Y.-T.; Liu, Y.-H.; Sun, L.-Q. Salvianolic Acid B Inhibits the Development of Diabetic Peripheral Neuropathy by Suppressing Autophagy and Apoptosis. J. Pharm. Pharmacol. 2019, 71, 417–428. [Google Scholar] [CrossRef] [PubMed]
- Yin, Y.; Qu, H.; Yang, Q.; Fang, Z.; Gao, R. Astragaloside IV Alleviates Schwann Cell Injury in Diabetic Peripheral Neuropathy by Regulating microRNA-155-Mediated Autophagy. Phytomed. Int. J. Phytother. Phytopharm. 2021, 92, 153749. [Google Scholar] [CrossRef] [PubMed]
- He, W.; Wan, H.; Hu, L.; Chen, P.; Wang, X.; Huang, Z.; Yang, Z.-H.; Zhong, C.-Q.; Han, J. Gasdermin D Is an Executor of Pyroptosis and Required for Interleukin-1β Secretion. Cell Res. 2015, 25, 1285–1298. [Google Scholar] [CrossRef] [PubMed]
- Fricker, M.; Tolkovsky, A.M.; Borutaite, V.; Coleman, M.; Brown, G.C. Neuronal Cell Death. Physiol. Rev. 2018, 98, 68. [Google Scholar] [CrossRef] [PubMed]
- Kovacs, S.B.; Miao, E.A. Gasdermins: Effectors of Pyroptosis. Trends Cell Biol. 2017, 27, 673–684. [Google Scholar] [CrossRef]
- Yu, P.; Zhang, X.; Liu, N.; Tang, L.; Peng, C.; Chen, X. Pyroptosis: Mechanisms and Diseases. Signal Transduct. Target. Ther. 2021, 6, 128. [Google Scholar] [CrossRef]
- Platnich, J.M.; Muruve, D.A. NOD-like Receptors and Inflammasomes: A Review of Their Canonical and Non-Canonical Signaling Pathways. Arch. Biochem. Biophys. 2019, 670, 4–14. [Google Scholar] [CrossRef] [PubMed]
- Baker, P.J.; Boucher, D.; Bierschenk, D.; Tebartz, C.; Whitney, P.G.; D’Silva, D.B.; Tanzer, M.C.; Monteleone, M.; Robertson, A.A.B.; Cooper, M.A.; et al. NLRP3 Inflammasome Activation Downstream of Cytoplasmic LPS Recognition by Both Caspase-4 and Caspase-5. Eur. J. Immunol. 2015, 45, 2918–2926. [Google Scholar] [CrossRef] [PubMed]
- Yang, D.; He, Y.; Muñoz-Planillo, R.; Liu, Q.; Núñez, G. Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock. Immunity 2015, 43, 923–932. [Google Scholar] [CrossRef] [PubMed]
- Che, H.; Li, H.; Li, Y.; Wang, Y.; Yang, Z.; Wang, R.; Wang, L. Melatonin Exerts Neuroprotective Effects by Inhibiting Neuronal Pyroptosis and Autophagy in STZ-induced Diabetic Mice. FASEB J. 2020, 34, 14042–14054. [Google Scholar] [CrossRef]
- Wang, L.-Q.; Zheng, Y.-Y.; Zhou, H.-J.; Zhang, X.-X.; Wu, P.; Zhu, S.-M. LncRNA-Fendrr Protects against the Ubiquitination and Degradation of NLRC4 Protein through HERC2 to Regulate the Pyroptosis of Microglia. Mol. Med. 2021, 27, 39. [Google Scholar] [CrossRef] [PubMed]
- Li, D.-X.; Wang, C.-N.; Wang, Y.; Ye, C.-L.; Jiang, L.; Zhu, X.-Y.; Liu, Y.-J. NLRP3 Inflammasome-Dependent Pyroptosis and Apoptosis in Hippocampus Neurons Mediates Depressive-like Behavior in Diabetic Mice. Behav. Brain Res. 2020, 391, 112684. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Cai, S.; Zhao, J.; Xu, K.; Ji, H.; Wu, C.; Xiao, J.; Wu, Y. Advances in the Relationship between Pyroptosis and Diabetic Neuropathy. Front. Cell Dev. Biol. 2021, 9, 753660. [Google Scholar] [CrossRef] [PubMed]
- Hong, P.; Li, F.-X.; Gu, R.-N.; Fang, Y.-Y.; Lai, L.-Y.; Wang, Y.-W.; Tao, T.; Xu, S.-Y.; You, Z.-J.; Zhang, H.-F. Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice. Neural Plast. 2018, 2018, 9163521. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.; Li, W.; Zhang, X.; Chung, S.L.; Dai, J.; Jin, Z. Tauroursodeoxycholic Acid Protects Schwann Cells from High Glucose–Induced Cytotoxicity by Targeting NLRP3 to Regulate Cell Migration and Pyroptosis. Biotechnol. Appl. Biochem. 2024, 71, 28–37. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Huang, S.; Zhuang, Z.; Han, X.; Xie, M.; Yu, S.; Hua, M.; Liang, Z.; Meng, C.; Yin, L.; et al. Lipin2 Ameliorates Diabetic Encephalopathy via Suppressing JNK/ERK-Mediated NLRP3 Inflammasome Overactivation. Int. Immunopharmacol. 2023, 118, 109930. [Google Scholar] [CrossRef] [PubMed]
- Meng, X.-F.; Wang, X.-L.; Tian, X.-J.; Yang, Z.-H.; Chu, G.-P.; Zhang, J.; Li, M.; Shi, J.; Zhang, C. Nod-Like Receptor Protein 1 Inflammasome Mediates Neuron Injury under High Glucose. Mol. Neurobiol. 2014, 49, 673–684. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Ji, S.; Xu, Y.; Zhang, C.-J. The Regulation and Modification of GSDMD Signaling in Diseases. Front. Immunol. 2022, 13, 893912. [Google Scholar] [CrossRef] [PubMed]
- Zhan, T.; Tang, S.; Du, J.; Liu, J.; Yu, B.; Yang, Y.; Xie, Y.; Qiu, Y.; Li, G.; Gao, Y. Implication of lncRNA MSTRG.81401 in Hippocampal Pyroptosis Induced by P2X7 Receptor in Type 2 Diabetic Rats with Neuropathic Pain Combined with Depression. Int. J. Mol. Sci. 2024, 25, 1186. [Google Scholar] [CrossRef] [PubMed]
- Wang, Q.-Q.; Wang, M.; Li, Y.; Liu, Y.-H.; Sun, L.-Q. Attenuation of Oxidative Stress-Induced Cell Apoptosis and Pyroptosis in RSC96 Cells by Salvianolic Acid B. Chin. J. Integr. Med. 2022, 28, 243–248. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.-C.; Chu, L.-W.; Chen, J.-Y.; Hsieh, S.-L.; Chang, Y.-C.; Dai, Z.-K.; Wu, B.-N. Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation. Cells 2020, 9, 1948. [Google Scholar] [CrossRef] [PubMed]
- Shi, L.; Hu, Q.; Li, L.; Yang, R.; Xu, X.; Du, J.; Zou, L.; Li, G.; Liu, S.; Li, G.; et al. Beneficial Effects of lncRNA-UC.360+ shRNA on Diabetic Cardiac Sympathetic Damage via NLRP3 Inflammasome-Induced Pyroptosis in Stellate Ganglion. ACS Omega 2022, 7, 27714–27721. [Google Scholar] [CrossRef] [PubMed]
- Vo, T.; Rice, A.S.C.; Dworkin, R.H. Non-Steroidal Anti-Inflammatory Drugs for Neuropathic Pain: How Do We Explain Continued Widespread Use? Pain 2009, 143, 169–171. [Google Scholar] [CrossRef] [PubMed]
- Joshi, R.P.; Negi, G.; Kumar, A.; Pawar, Y.B.; Munjal, B.; Bansal, A.K.; Sharma, S.S. SNEDDS Curcumin Formulation Leads to Enhanced Protection from Pain and Functional Deficits Associated with Diabetic Neuropathy: An Insight into Its Mechanism for Neuroprotection. Nanomed. Nanotechnol. Biol. Med. 2013, 9, 776–785. [Google Scholar] [CrossRef] [PubMed]
- Khoury, M.K.; Gupta, K.; Franco, S.R.; Liu, B. Necroptosis in the Pathophysiology of Disease. Am. J. Pathol. 2020, 190, 272–285. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Chen, W.; He, L.; Liu, D.; Zhao, L.; Wang, X. A Glimpse of Necroptosis and Diseases. Biomed. Pharmacother. 2022, 156, 113925. [Google Scholar] [CrossRef] [PubMed]
- Cheng, Y.; Kou, Y.; Wang, J.; Wang, Y.; Rong, W.; Han, H.; Zhang, G. 5-Hydroxytryptamine 4 Receptor Agonist Attenuates Diabetic Enteric Neuropathy through Inhibition of the Receptor-Interacting Protein Kinase 3 Pathway. Am. J. Pathol. 2024, 194, 785–795. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed]
- Jiang, X.; Stockwell, B.R.; Conrad, M. Ferroptosis: Mechanisms, Biology and Role in Disease. Nat. Rev. Mol. Cell Biol. 2021, 22, 266–282. [Google Scholar] [CrossRef]
- Lei, G.; Zhuang, L.; Gan, B. Targeting Ferroptosis as a Vulnerability in Cancer. Nat. Rev. Cancer 2022, 22, 381–396. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Dai, S.; Zheng, W.; Chen, W.; Li, J.; Chen, X.; Zhou, S.; Yang, R. Identification and Verification of Ferroptosis-Related Genes in Diabetic Foot Using Bioinformatics Analysis. Int. Wound J. 2023, 20, 3191–3203. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.-D.; Yang, Y.-Y. Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications. Front. Endocrinol. 2022, 13, 853822. [Google Scholar] [CrossRef] [PubMed]
- Wu, K.-Y.; Deng, F.; Mao, X.-Y.; Zhou, D.; Shen, W.-G. Ferroptosis Involves in Schwann Cell Death in Diabetic Peripheral Neuropathy. Open Med. 2023, 18, 20230809. [Google Scholar] [CrossRef] [PubMed]
- Tang, G.; Pi, L.; Guo, H.; Hu, Z.; Zhou, C.; Hu, Q.; Peng, H.; Xiao, Z.; Zhang, Z.; Wang, M.; et al. Naringin Relieves Diabetic Cardiac Autonomic Neuropathy Mediated by P2Y(14) Receptor in Superior Cervical Ganglion. Front. Pharmacol. 2022, 13, 873090. [Google Scholar] [CrossRef]
- Chen, J.; Li, X.; Liu, H.; Zhong, D.; Yin, K.; Li, Y.; Zhu, L.; Xu, C.; Li, M.; Wang, C. Bone Marrow Stromal Cell-Derived Exosomal Circular RNA Improves Diabetic Foot Ulcer Wound Healing by Activating the Nuclear Factor Erythroid 2-Related Factor 2 Pathway and Inhibiting Ferroptosis. Diabet. Med. 2023, 40, e15031. [Google Scholar] [CrossRef] [PubMed]
- Wang, B.; Zhu, S.; Guo, M.; Ma, R.-D.; Tang, Y.-L.; Nie, Y.-X.; Gu, H.-F. Artemisinin Ameliorates Cognitive Decline by Inhibiting Hippocampal Neuronal Ferroptosis via Nrf2 Activation in T2DM Mice. Mol. Med. 2024, 30, 35. [Google Scholar] [CrossRef] [PubMed]
- Shi, Y.-S.; Chen, J.-C.; Lin, L.; Cheng, Y.-Z.; Zhao, Y.; Zhang, Y.; Pan, X.-D. Dendrobine Rescues Cognitive Dysfunction in Diabetic Encephalopathy by Inhibiting Ferroptosis via Activating Nrf2/GPX4 Axis. Phytomedicine 2023, 119, 154993. [Google Scholar] [CrossRef] [PubMed]
- Chen, J.; Guo, P.; Han, M.; Chen, K.; Qin, J.; Yang, F. Cognitive Protection of Sinomenine in Type 2 Diabetes Mellitus through Regulating the EGF /Nrf2/ HO -1 Signaling, the Microbiota-gut-brain Axis, and Hippocampal Neuron Ferroptosis. Phytother. Res. 2023, 37, 3323–3341. [Google Scholar] [CrossRef] [PubMed]
- Xie, Z.; Wang, X.; Luo, X.; Yan, J.; Zhang, J.; Sun, R.; Luo, A.; Li, S. Activated AMPK Mitigates Diabetes-Related Cognitive Dysfunction by Inhibiting Hippocampal Ferroptosis. Biochem. Pharmacol. 2023, 207, 115374. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.; Li, Y.; He, S.; Jiang, T.; Wang, N.; Du, M.; Cheng, B.; Gao, W.; Li, Y.; Wang, Q. Caveolin-1 Alleviates Diabetes-Associated Cognitive Dysfunction through Modulating Neuronal Ferroptosis-Mediated Mitochondrial Homeostasis. Antioxid. Redox Signal. 2022, 37, 867–886. [Google Scholar] [CrossRef] [PubMed]
- Guo, T.; Yu, Y.; Yan, W.; Zhang, M.; Yi, X.; Liu, N.; Cui, X.; Wei, X.; Sun, Y.; Wang, Z.; et al. Erythropoietin Ameliorates Cognitive Dysfunction in Mice with Type 2 Diabetes Mellitus via Inhibiting Iron Overload and Ferroptosis. Exp. Neurol. 2023, 365, 114414. [Google Scholar] [CrossRef] [PubMed]
- An, J.-R.; Su, J.-N.; Sun, G.-Y.; Wang, Q.-F.; Fan, Y.-D.; Jiang, N.; Yang, Y.-F.; Shi, Y. Liraglutide Alleviates Cognitive Deficit in Db/Db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis. Neurochem. Res. 2022, 47, 279–294. [Google Scholar] [CrossRef] [PubMed]
- Hao, L.; Mi, J.; Song, L.; Guo, Y.; Li, Y.; Yin, Y.; Zhang, C. SLC40A1 Mediates Ferroptosis and Cognitive Dysfunction in Type 1 Diabetes. Neuroscience 2021, 463, 216–226. [Google Scholar] [CrossRef] [PubMed]
- Wang, N.; Zhao, Y.; Wu, M.; Li, N.; Yan, C.; Guo, H.; Li, Q.; Li, Q.; Wang, Q. Gemfibrozil Alleviates Cognitive Impairment by Inhibiting Ferroptosis of Astrocytes via Restoring the Iron Metabolism and Promoting Antioxidant Capacity in Type 2 Diabetes. Mol. Neurobiol. 2024, 61, 1187–1201. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.; Feng, S.; Li, Q.; Song, Z.; He, J.; Yang, S.; Yan, C.; Ling, H. Dihydromyricetin Alleviates Hippocampal Ferroptosis in Type 2 Diabetic Cognitive Impairment Rats via Inhibiting the JNK-Inflammatory Factor Pathway. Neurosci. Lett. 2023, 812, 137404. [Google Scholar] [CrossRef] [PubMed]
- Huang, P.; Chen, G.; Jin, W.; Mao, K.; Wan, H.; He, Y. Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases. Int. J. Mol. Sci. 2022, 23, 7292. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Jiao, Y.; Yu, Y.; Wang, G.; Yu, Y. Hydrogen-rich Medium Alleviates High Glucose-induced Oxidative Stress and Parthanatos in Rat Schwann Cells in Vitro. Mol. Med. Rep. 2019, 19, 338–344. [Google Scholar] [CrossRef]
- Fernández, A.; Ordóñez, R.; Reiter, R.J.; González-Gallego, J.; Mauriz, J.L. Melatonin and Endoplasmic Reticulum Stress: Relation to Autophagy and Apoptosis. J. Pineal Res. 2015, 59, 292–307. [Google Scholar] [CrossRef] [PubMed]
- Mok, J.X.; Ooi, J.H.; Ng, K.Y.; Koh, R.Y.; Chye, S.M. A New Prospective on the Role of Melatonin in Diabetes and Its Complications. Horm. Mol. Biol. Clin. Investig. 2019, 40, 20190036. [Google Scholar] [CrossRef] [PubMed]
- Chang, W.; Li, P. Copper and Diabetes: Current Research and Prospect. Mol. Nutr. Food Res. 2023, 67, 2300468. [Google Scholar] [CrossRef] [PubMed]
Mechanism of Cell Death | Key Players | Involvement in DN | Potential Therapeutic Targets | Agents | References |
---|---|---|---|---|---|
Apoptosis | BCL-2 family proteins, Cytochrome c, Caspases | Apoptosis occurs in neurons and glial cells, leading to demyelination and neuronal damage | Antioxidants, Inhibition of death pathways, Anti-inflammatory agents | Alpha-lipoic acid (ALA) | [59,60,61] |
Autophagy | Autophagy-related proteins (ATGs), Beclin-1, LC3 | Controversial effect in DN, both overactivation and inhibition reported | Modulation of autophagy levels, Inhibition of mTOR pathway | Arctigenin (inhibitor of mTOR) | [87] |
Pyroptosis | Inflammasomes, Caspase-1, GSDMD | Associated with neuroinflammation and neuronal damage in DN | Inflammasome inhibitors, Caspase inhibitors, GSDMD inhibitors | MCC950 (NLRP3 inflammasome inhibitor) | [105] |
Ferroptosis | GPX4, System Xc-, Iron-metabolism-related proteins | Potential role in neuronal damage in DN | Activation of Nrf2 pathway, Inhibition of lipid peroxidation | Liraglutide (promotes GPX4 and SLC7A11 expression) | [133] |
Necroptosis | RIPK1, RIPK3, MLKL | Less understood in DN, but associated with diabetic nephropathy | Inhibition of RIPK1/RIPK3/MLKL pathway | N/A | N/A |
Parthanatos | PARP-1, AIF | Triggered by DNA damage in DN | Reduction in PAR levels, Prevention of AIF translocation | Hydrogen-rich medium | [138] |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ye, S.; Cheng, Z.; Zhuo, D.; Liu, S. Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies. Int. J. Mol. Sci. 2024, 25, 8126. https://doi.org/10.3390/ijms25158126
Ye S, Cheng Z, Zhuo D, Liu S. Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies. International Journal of Molecular Sciences. 2024; 25(15):8126. https://doi.org/10.3390/ijms25158126
Chicago/Turabian StyleYe, Shang, Zilin Cheng, Dongye Zhuo, and Shuangmei Liu. 2024. "Different Types of Cell Death in Diabetic Neuropathy: A Focus on Mechanisms and Therapeutic Strategies" International Journal of Molecular Sciences 25, no. 15: 8126. https://doi.org/10.3390/ijms25158126