Amyloid precursor protein dosage normalization rescues neurogenesis and Alzheimer’s Disease phenotypes associated with Down Syndrome
Main Article Content
Abstract
Down Syndrome (DS) is the most abundant genetic form of mental retardation. It is caused by the triplication of partial or complete human chromosome 21 (HSA21). The molecular mechanisms of DS are not fully understood. Amyloid precursor protein (APP) resides on HSA21 and is triplicated in DS. While it is not thought to be a part of the “Down syndrome Critical Region”, APP plays a role in developmental and post-natal neurogenesis and synaptic plasticity, thus, its triplication may affect cortical development in DS. Further, mutations in APP cause familial Alzheimer’s disease (AD). However, whether APP overdose is sufficient or required for the development of Alzheimer’s disease in DS is not fully elucidated. Here, we addressed the role of APP overdose in neuronal development and AD pathology. Using DS patient-derived induced pluripotent stem cells in which one copy of APP was silenced using CRISPR-Cas9, we examined developmenta neurogenesis, AD-related pathology and the expression levels of genes on HSA21 that are implicated in DS, neurodegeneration and inflammation. Amyloid precursor protein triplication, in DS induced pluripotent stem cells, led to reduced stem cell proliferation, enhanced differentiation into neurons, increased amyloid pathology, and altered protein levels of selected genes on HSA21. Correction of APP gene dosage rescued the altered neurogenesis phenotype and reduced pathological amyloidogenic processing. These data highlight APP dosage as a key regulator of neuronal maturation and AD pathology in DS, suggesting therapeutic value in targeting APP expression to mitigate neurodevelopmental and neurodegenerative features of the disorder.
Keywords:
Down Syndrome, Amyloid precursor protein, Neurogenesis, Alzheimer’s disease
Article Details
How to Cite
PATEL, Deepika; RAKOWIECKI, Karen; LAZAROV, Orly.
Amyloid precursor protein dosage normalization rescues neurogenesis and Alzheimer’s Disease phenotypes associated with Down Syndrome.
Medical Research Archives, [S.l.], v. 14, n. 6, july 2026.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/7577>. Date accessed: 02 july 2026.
Keywords
Down Syndrome, Amyloid precursor protein, Neurogenesis, Alzheimer's disease
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Ruparelia A, Pearn ML, Mobley WC. Aging and intellectual disability: insights from mouse models of Down syndrome. Dev Disabil Res Rev. 2013;18(1):43-50. doi:10.1002/ddrr.1127
2. Patkee PA, Baburamani AA, Kyriakopoulou V, et al. Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment. NeuroImage Clin. 2020;25:102139. doi:10.1016/j.nicl.2019.102139
3. Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012;13(12):844-858. doi:10.1038/nrn3314
4. Korbel JO, Tirosh-Wagner T, Urban AE, et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci U S A. 2009;106(29):12031-12036. doi:10.1073/pnas.0813248106
5. Müller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci. 2017;18(5):281-298. doi:10.1038/nrn.2017.29
6. Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ. A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci Off J Soc Neurosci. 2007;27(52):14459-14469. doi:10.1523/JNEUROSCI.4701-07.2007
7. Coronel R, López-Alonso V, Gallego MI, Liste I. Low Levels of Amyloid Precursor Protein (APP) Promote Neurogenesis and Decrease Gliogenesis in Human Neural Stem Cells. Int J Mol Sci. 2023;24(19):14635. doi:10.3390/ijms241914635
8. Caillé I, Allinquant B, Dupont E, et al. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Dev Camb Engl. 2004;131(9):2173-2181. doi:10.1242/dev.01103
9. Rice HC, Townsend M, Bai J, et al. Pancortins interact with amyloid precursor protein and modulate cortical cell migration. Dev Camb Engl. 2012;139(21):3986-3996. doi:10.1242/dev.082909
10. Müller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci. 2017;18(5):281-298. doi:10.1038/nrn.2017.29
11. Lee SH, Kang J, Ho A, Watanabe H, Bolshakov VY, Shen J. APP Family Regulates Neuronal Excitability and Synaptic Plasticity but Not Neuronal Survival. Neuron. 2020;108(4):676-690.e8. doi:10.1016/j.neuron.2020.08.011
12. Klevanski M, Herrmann U, Weyer SW, et al. The APP Intracellular Domain Is Required for Normal Synaptic Morphology, Synaptic Plasticity, and Hippocampus-Dependent Behavior. J Neurosci. 2015;35(49):16018-16033. doi:10.1523/JNEUROSCI.2009-15.2015
13. Hick M, Herrmann U, Weyer SW, et al. Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity. Acta Neuropathol (Berl). 2015;129(1):21-37. doi:10.1007/s00401-014-1368-x
14. Li H, Wang Z, Wang B, et al. Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J Biol Chem. 2010;285(40):30598-30605. doi:10.1074/jbc.M110.137729
15. Lazarov O, Demars MP. All in the Family: How the APPs Regulate Neurogenesis. Front Neurosci. 2012;6:81. doi:10.3389/fnins.2012.00081
16. Zhou Z dong, Chan CH shan, Ma Q hong, Xu X hong, Xiao Z cheng, Tan EK. The roles of amyloid precursor protein (APP) in neurogenesis, implications to pathogenesis and therapy of Alzheimer disease (AD). Cell Adhes Migr. 2011;5(4):280-292. doi:10.4161/cam.5.4.16986
17. Wang B, Wang Z, Sun L, et al. The Amyloid Precursor Protein Controls Adult Hippocampal Neurogenesis through GABAergic Interneurons. J Neurosci. 2014;34(40):13314-13325. doi:10.1523/JNEUROSCI.2848-14.2014
18. Demars MP, Bartholomew A, Strakova Z, Lazarov O. Soluble amyloid precursor protein: a novel proliferation factor of adult progenitor cells of ectodermal and mesodermal origin. Stem Cell Res Ther. 2011;2(4):36. doi:10.1186/scrt77
19. Demars MP, Hollands C, Zhao KDT, Lazarov O. Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation. Neurobiol Aging. 2013;34(10):2431-2440. doi:10.1016/j.neurobiolaging.2013.04.016
20. Shabani K, Pigeon J, Benaissa Touil Zariouh M, et al. The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci Adv. 2023;9(24):eadd5002. doi:10.1126/sciadv.add5002
21. Ovchinnikov DA, Korn O, Virshup I, Wells CA, Wolvetang EJ. The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons. Stem Cell Rep. 2018;11(1):32-42. doi:10.1016/j.stemcr.2018.05.004
22. Sosa LJ, Postma NL, Estrada-Bernal A, et al. Dosage of amyloid precursor protein affects axonal contact guidance in Down syndrome. FASEB J Off Publ Fed Am Soc Exp Biol. 2014;28(1):195-205. doi:10.1096/fj.13-232686
23. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81(2):741-766. doi:10.1152/physrev.2001.81.2.741
24. Maure-Blesa L, Carmona-Iragui M, Lott I, et al. The history of Down syndrome-associated Alzheimer’s disease; past, present, and future. Alzheimers Dement J Alzheimers Assoc. 2025;21(6):e70158. doi:10.1002/alz.70158
25. Zigman WB, Lott IT. Alzheimer’s disease in Down syndrome: Neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007;13(3):237-246. doi:10.1002/mrdd.20163
26. Ovchinnikov DA, Korn O, Virshup I, Wells CA, Wolvetang EJ. The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons. Stem Cell Rep. 2018;11(1):32-42. doi:10.1016/j.stemcr.2018.05.004
27. Wu CI, Vinton EA, Pearse RV, et al. APP and DYRK1A regulate axonal and synaptic vesicle protein networks and mediate Alzheimer’s pathology in trisomy 21 neurons. Mol Psychiatry. 2022;27(4):1970-1989. doi:10.1038/s41380-022-01454-5
28. Lu HE, Yang YC, Chen SM, et al. Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells. Exp Cell Res. 2013;319(4):498-505. doi:10.1016/j.yexcr.2012.09.017
29. Utagawa EC, Moreno DG, Schafernak KT, et al. Neurogenesis and neuronal differentiation in the postnatal frontal cortex in Down syndrome. Acta Neuropathol Commun. 2022;10(1):86. doi:10.1186/s40478-022-01385-w
30. Hernández-Ortega K, Canul-Euan AA, Solis-Paredes JM, et al. S100B actions on glial and neuronal cells in the developing brain: an overview. Front Neurosci. 2024;18. doi:10.3389/fnins.2024.1425525
31. Shapiro LA, Bialowas-McGoey LA, Whitaker-Azmitia PM. Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer’s Disease: Studies in an S100B Overexpressing Mouse Model. Cardiovasc Psychiatry Neurol. 2010;2010:153657. doi:10.1155/2010/153657
32. Matsui Lee IS, Suzuki M, Hayashi N, et al. Copper-dependent formation of disulfide-linked dimer of S100B protein. Arch Biochem Biophys. 2000;374(2):137-141. doi:10.1006/abbi.1999.1595
33. Thulin E, Kesvatera T, Linse S. Molecular Determinants of S100B Oligomer Formation. PLOS ONE. 2011;6(3):e14768. doi:10.1371/journal.pone.0014768
34. Langeh U, Singh S. Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders. Curr Neuropharmacol. 2021;19(2):265-277. doi:10.2174/1570159X18666200729100427
35. Lu J, Esposito G, Scuderi C, et al. S100B and APP Promote a Gliocentric Shift and Impaired Neurogenesis in Down Syndrome Neural Progenitors. PLOS ONE. 2011;6(7):e22126. doi:10.1371/journal.pone.0022126
36. Stagni F, Bartesaghi R. The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives. Front Cell Neurosci. 2022;16:903729. doi:10.3389/fncel.2022.903729
37. Shabani K, Pigeon J, Benaissa Touil Zariouh M, et al. The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci Adv. 9(24):eadd5002. doi:10.1126/sciadv.add5002
38. Chen XQ. A pilot exploration with Posiphen to normalize amyloid precursor protein in Down syndrome. Neural Regen Res. 2021;16(12):2420-2421. doi:10.4103/1673-5374.313044
39. Chen XQ, Salehi A, Pearn ML, et al. Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model. Alzheimers Dement J Alzheimers Assoc. 2021;17(2):271-292. doi:10.1002/alz.12185
40. Ryoo SR, Jeong HK, Radnaabazar C, et al. DYRK1A-mediated Hyperphosphorylation of Tau. J Biol Chem. 2007;282(48):34850-34857. doi:10.1074/jbc.M707358200
41. Duchon A, Herault Y. DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome. Front Behav Neurosci. 2016;10:104. doi:10.3389/fnbeh.2016.00104
42. Griffin WST, Sheng JG, McKenzie JE, et al. Life-long overexpression of S100β in Down’s syndrome: implications for Alzheimer pathogenesis. Neurobiol Aging. 1998;19(5):401-405. doi:10.1016/S0197-4580(98)00074-8
43. Guan T, Guo Y, Zhou T, et al. Oxidized SOD1 accelerates cellular senescence in neural stem cells. Stem Cell Res Ther. 2024;15(1):55. doi:10.1186/s13287-024-03669-5
44. Taylor JM, Crack PJ. Impact of Oxidative Stress on Neuronal Survival. Clin Exp Pharmacol Physiol. 2004;31(7):397-406. doi:10.1111/j.1440-1681.2004.04017.x
45. Chidambaram SB, Anand N, Varma SR, et al. Superoxide dismutase and neurological disorders. IBRO Neurosci Rep. 2024;16:373-394. doi:10.1016/j.ibneur.2023.11.007
2. Patkee PA, Baburamani AA, Kyriakopoulou V, et al. Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment. NeuroImage Clin. 2020;25:102139. doi:10.1016/j.nicl.2019.102139
3. Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. 2012;13(12):844-858. doi:10.1038/nrn3314
4. Korbel JO, Tirosh-Wagner T, Urban AE, et al. The genetic architecture of Down syndrome phenotypes revealed by high-resolution analysis of human segmental trisomies. Proc Natl Acad Sci U S A. 2009;106(29):12031-12036. doi:10.1073/pnas.0813248106
5. Müller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci. 2017;18(5):281-298. doi:10.1038/nrn.2017.29
6. Young-Pearse TL, Bai J, Chang R, Zheng JB, LoTurco JJ, Selkoe DJ. A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. J Neurosci Off J Soc Neurosci. 2007;27(52):14459-14469. doi:10.1523/JNEUROSCI.4701-07.2007
7. Coronel R, López-Alonso V, Gallego MI, Liste I. Low Levels of Amyloid Precursor Protein (APP) Promote Neurogenesis and Decrease Gliogenesis in Human Neural Stem Cells. Int J Mol Sci. 2023;24(19):14635. doi:10.3390/ijms241914635
8. Caillé I, Allinquant B, Dupont E, et al. Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone. Dev Camb Engl. 2004;131(9):2173-2181. doi:10.1242/dev.01103
9. Rice HC, Townsend M, Bai J, et al. Pancortins interact with amyloid precursor protein and modulate cortical cell migration. Dev Camb Engl. 2012;139(21):3986-3996. doi:10.1242/dev.082909
10. Müller UC, Deller T, Korte M. Not just amyloid: physiological functions of the amyloid precursor protein family. Nat Rev Neurosci. 2017;18(5):281-298. doi:10.1038/nrn.2017.29
11. Lee SH, Kang J, Ho A, Watanabe H, Bolshakov VY, Shen J. APP Family Regulates Neuronal Excitability and Synaptic Plasticity but Not Neuronal Survival. Neuron. 2020;108(4):676-690.e8. doi:10.1016/j.neuron.2020.08.011
12. Klevanski M, Herrmann U, Weyer SW, et al. The APP Intracellular Domain Is Required for Normal Synaptic Morphology, Synaptic Plasticity, and Hippocampus-Dependent Behavior. J Neurosci. 2015;35(49):16018-16033. doi:10.1523/JNEUROSCI.2009-15.2015
13. Hick M, Herrmann U, Weyer SW, et al. Acute function of secreted amyloid precursor protein fragment APPsα in synaptic plasticity. Acta Neuropathol (Berl). 2015;129(1):21-37. doi:10.1007/s00401-014-1368-x
14. Li H, Wang Z, Wang B, et al. Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J Biol Chem. 2010;285(40):30598-30605. doi:10.1074/jbc.M110.137729
15. Lazarov O, Demars MP. All in the Family: How the APPs Regulate Neurogenesis. Front Neurosci. 2012;6:81. doi:10.3389/fnins.2012.00081
16. Zhou Z dong, Chan CH shan, Ma Q hong, Xu X hong, Xiao Z cheng, Tan EK. The roles of amyloid precursor protein (APP) in neurogenesis, implications to pathogenesis and therapy of Alzheimer disease (AD). Cell Adhes Migr. 2011;5(4):280-292. doi:10.4161/cam.5.4.16986
17. Wang B, Wang Z, Sun L, et al. The Amyloid Precursor Protein Controls Adult Hippocampal Neurogenesis through GABAergic Interneurons. J Neurosci. 2014;34(40):13314-13325. doi:10.1523/JNEUROSCI.2848-14.2014
18. Demars MP, Bartholomew A, Strakova Z, Lazarov O. Soluble amyloid precursor protein: a novel proliferation factor of adult progenitor cells of ectodermal and mesodermal origin. Stem Cell Res Ther. 2011;2(4):36. doi:10.1186/scrt77
19. Demars MP, Hollands C, Zhao KDT, Lazarov O. Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation. Neurobiol Aging. 2013;34(10):2431-2440. doi:10.1016/j.neurobiolaging.2013.04.016
20. Shabani K, Pigeon J, Benaissa Touil Zariouh M, et al. The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci Adv. 2023;9(24):eadd5002. doi:10.1126/sciadv.add5002
21. Ovchinnikov DA, Korn O, Virshup I, Wells CA, Wolvetang EJ. The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons. Stem Cell Rep. 2018;11(1):32-42. doi:10.1016/j.stemcr.2018.05.004
22. Sosa LJ, Postma NL, Estrada-Bernal A, et al. Dosage of amyloid precursor protein affects axonal contact guidance in Down syndrome. FASEB J Off Publ Fed Am Soc Exp Biol. 2014;28(1):195-205. doi:10.1096/fj.13-232686
23. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001;81(2):741-766. doi:10.1152/physrev.2001.81.2.741
24. Maure-Blesa L, Carmona-Iragui M, Lott I, et al. The history of Down syndrome-associated Alzheimer’s disease; past, present, and future. Alzheimers Dement J Alzheimers Assoc. 2025;21(6):e70158. doi:10.1002/alz.70158
25. Zigman WB, Lott IT. Alzheimer’s disease in Down syndrome: Neurobiology and risk. Ment Retard Dev Disabil Res Rev. 2007;13(3):237-246. doi:10.1002/mrdd.20163
26. Ovchinnikov DA, Korn O, Virshup I, Wells CA, Wolvetang EJ. The Impact of APP on Alzheimer-like Pathogenesis and Gene Expression in Down Syndrome iPSC-Derived Neurons. Stem Cell Rep. 2018;11(1):32-42. doi:10.1016/j.stemcr.2018.05.004
27. Wu CI, Vinton EA, Pearse RV, et al. APP and DYRK1A regulate axonal and synaptic vesicle protein networks and mediate Alzheimer’s pathology in trisomy 21 neurons. Mol Psychiatry. 2022;27(4):1970-1989. doi:10.1038/s41380-022-01454-5
28. Lu HE, Yang YC, Chen SM, et al. Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells. Exp Cell Res. 2013;319(4):498-505. doi:10.1016/j.yexcr.2012.09.017
29. Utagawa EC, Moreno DG, Schafernak KT, et al. Neurogenesis and neuronal differentiation in the postnatal frontal cortex in Down syndrome. Acta Neuropathol Commun. 2022;10(1):86. doi:10.1186/s40478-022-01385-w
30. Hernández-Ortega K, Canul-Euan AA, Solis-Paredes JM, et al. S100B actions on glial and neuronal cells in the developing brain: an overview. Front Neurosci. 2024;18. doi:10.3389/fnins.2024.1425525
31. Shapiro LA, Bialowas-McGoey LA, Whitaker-Azmitia PM. Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer’s Disease: Studies in an S100B Overexpressing Mouse Model. Cardiovasc Psychiatry Neurol. 2010;2010:153657. doi:10.1155/2010/153657
32. Matsui Lee IS, Suzuki M, Hayashi N, et al. Copper-dependent formation of disulfide-linked dimer of S100B protein. Arch Biochem Biophys. 2000;374(2):137-141. doi:10.1006/abbi.1999.1595
33. Thulin E, Kesvatera T, Linse S. Molecular Determinants of S100B Oligomer Formation. PLOS ONE. 2011;6(3):e14768. doi:10.1371/journal.pone.0014768
34. Langeh U, Singh S. Targeting S100B Protein as a Surrogate Biomarker and its Role in Various Neurological Disorders. Curr Neuropharmacol. 2021;19(2):265-277. doi:10.2174/1570159X18666200729100427
35. Lu J, Esposito G, Scuderi C, et al. S100B and APP Promote a Gliocentric Shift and Impaired Neurogenesis in Down Syndrome Neural Progenitors. PLOS ONE. 2011;6(7):e22126. doi:10.1371/journal.pone.0022126
36. Stagni F, Bartesaghi R. The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives. Front Cell Neurosci. 2022;16:903729. doi:10.3389/fncel.2022.903729
37. Shabani K, Pigeon J, Benaissa Touil Zariouh M, et al. The temporal balance between self-renewal and differentiation of human neural stem cells requires the amyloid precursor protein. Sci Adv. 9(24):eadd5002. doi:10.1126/sciadv.add5002
38. Chen XQ. A pilot exploration with Posiphen to normalize amyloid precursor protein in Down syndrome. Neural Regen Res. 2021;16(12):2420-2421. doi:10.4103/1673-5374.313044
39. Chen XQ, Salehi A, Pearn ML, et al. Targeting increased levels of APP in Down syndrome: Posiphen-mediated reductions in APP and its products reverse endosomal phenotypes in the Ts65Dn mouse model. Alzheimers Dement J Alzheimers Assoc. 2021;17(2):271-292. doi:10.1002/alz.12185
40. Ryoo SR, Jeong HK, Radnaabazar C, et al. DYRK1A-mediated Hyperphosphorylation of Tau. J Biol Chem. 2007;282(48):34850-34857. doi:10.1074/jbc.M707358200
41. Duchon A, Herault Y. DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome. Front Behav Neurosci. 2016;10:104. doi:10.3389/fnbeh.2016.00104
42. Griffin WST, Sheng JG, McKenzie JE, et al. Life-long overexpression of S100β in Down’s syndrome: implications for Alzheimer pathogenesis. Neurobiol Aging. 1998;19(5):401-405. doi:10.1016/S0197-4580(98)00074-8
43. Guan T, Guo Y, Zhou T, et al. Oxidized SOD1 accelerates cellular senescence in neural stem cells. Stem Cell Res Ther. 2024;15(1):55. doi:10.1186/s13287-024-03669-5
44. Taylor JM, Crack PJ. Impact of Oxidative Stress on Neuronal Survival. Clin Exp Pharmacol Physiol. 2004;31(7):397-406. doi:10.1111/j.1440-1681.2004.04017.x
45. Chidambaram SB, Anand N, Varma SR, et al. Superoxide dismutase and neurological disorders. IBRO Neurosci Rep. 2024;16:373-394. doi:10.1016/j.ibneur.2023.11.007