Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis

Abstract

Recent studies have shown that cellular levels of polyamines (PAs) are significantly altered in neurodegenerative diseases. Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress, mitochondrial metabolism, cellular immunity, and ion channel functions. Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases. Therefore, in the current work, evidence was collected to determine the possible associations between cellular levels of PAs, and related enzymes and the development of several neurodegenerative diseases, which could provide a new idea for the treatment of neurodegenerative diseases in the future.

Keywords

polyamine / apoptosis / mitochondria / neurodegenerative disease

References

[1] MichaelAJ. Biosynthesis of polyamines and polyamine-containing molecules. Biochem J, 2016, 473(15): 2315-2329

[2] XuW, GaoL, LiT, et al.. Neuroprotective Role of Agmatine in Neurological Diseases. Curr Neuropharmacol, 2018, 16(9): 1296-1305

[3] Muñoz-EsparzaNC, Latorre-MoratallaML, Comas-BastéO, et al.. Polyamines in Food. Front Nutr, 2019, 6: 108

[4] BaeDH, LaneD, JanssonPJ, et al.. The old and new biochemistry of polyamines. Biochim Biophys Acta Gen Subj, 2018, 1862(9): 2053-2068

[5] RajeeveV, PearceW, CascanteM, et al.. Polyamine production is downstream and upstream of oncogenic PI3K signalling and contributes to tumour cell growth. Biochem J, 2013, 450(3): 619-628

[6] GuerraPR, LiuG, LemireS, et al.. Polyamine depletion has global effects on stress and virulence gene expression and affects HilA translation in Salmonella enterica serovar typhimurium. Res Microbiol, 2020, 171(3–4): 143-152

[7] SaundersFR, WallaceHM. Polyamine metabolism and cancer prevention. Biochem Soc Trans, 2007, 35: 364-368 Pt 2)

[8] CervelliM, AngelucciE, GermaniF, et al.. Inflammation, carcinogenesis and neurodegeneration studies in transgenic animal models for polyamine research. Amino Acids, 2014, 46(3): 521-530

[9] GuerraGP, RubinMA, MelloCF. Modulation of learning and memory by natural polyamines. Pharmacol Res, 2016, 112: 99-118

[10] GiladGM, GiladVH. Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats. Neurosci Lett, 2000, 296(2–3): 97-100

[11] GiladGM, GiladVH. Polyamines can protect against ischemia-induced nerve cell death in gerbil forebrain. Exp Neurol, 1991, 111(3): 349-355

[12] GiladGM, GiladVH. Polyamines in neurotrauma. Ubiquitous molecules in search of a function. Biochem Pharmacol, 1992, 44(3): 401-407

[13] SaikiS, SasazawaY, FujimakiM, et al.. A metabolic profile of polyamines in parkinson disease: A promising biomarker. Ann Neurol, 2019, 86(2): 251-263

[14] AminM, TangS, ShalamanovaL, et al.. Polyamine Biomarkers as Indicators of Human Disease. Biomarkers, 2021, 26(2): 77-94

[15] Sandusky-BeltranLA, KovalenkoA, MaC, et al.. Spermidine/spermine-N(1)-acetyltransferase ablation impacts tauopathy-induced polyamine stress response. Alzheimers Res Ther, 2019, 11(1): 58

[16] PolisB, KarasikD, SamsonAO. Alzheimer’s disease as a chronic maladaptive polyamine stress response. Aging (Albany NY), 2021, 13(7): 10770-10795

[17] LiuP, GuptaN, JingY, et al.. Age-related changes in polyamines in memory-associated brain structures in rats. Neuroscience, 2008, 155(3): 789-796

[18] KanMJ, LeeJE, WilsonJG, et al.. Arginine deprivation and immune suppression in a mouse model of Alzheimer’s disease. J Neurosci, 2015, 35(15): 5969-5982

[19] XuTT, LiH, DaiZ, et al.. Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice. Aging (Albany NY), 2020, 12(7): 6401-6414

[20] PolisB, SrikanthKD, ElliottE, et al.. L-Norvaline Reverses Cognitive Decline and Synaptic Loss in a Murine Model of Alzheimer’s Disease. Neurotherapeutics, 2018, 15(4): 1036-1054

[21] FischerM, RuhnauJ, SchulzeJ, et al.. Spermine and spermidine modulate T-cell function in older adults with and without cognitive decline ex vivo. Aging (Albany NY), 2020, 12(13): 13716-13739

[22] SequeiraA, GwadryFG, Ffrench-MullenJM, et al.. Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch Gen Psychiatry, 2006, 63(1): 35-48

[23] ChenGG, FioriLM, MoquinL, et al.. Evidence of altered polyamine concentrations in cerebral cortex of suicide completers. Neuropsychopharmacology, 2010, 35(7): 1477-1484

[24] LimonA, MamdaniF, HjelmBE, et al.. Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission. Neurosci Biobehav Rev, 2016, 66: 80-91

[25] VijayanB, RajV, NandakumarS, et al.. Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration. Cell Biol Toxicol, 2019, 35(2): 147-159

[26] RegunathanS, ReisDJ. Characterization of arginine decarboxylase in rat brain and liver: distinction from ornithine decarboxylase. J Neurochem, 2000, 74(5): 2201-2208

[27] GorbatyukOS, MilnerTA, WangG, et al.. Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei. Exp Neurol, 2001, 171(2): 235-245

[28] SezerA, GucluB, KazanciB, et al.. Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial. Turk Neurosurg, 2014, 24(2): 196-201

[29] KotagaleNR, TaksandeBG, InamdarNN. Neuro-protective offerings by agmatine. Neurotoxicology, 2019, 73: 228-245

[30] SongJ, HurBE, BokaraKK, et al.. Agmatine improves cognitive dysfunction and prevents cell death in a streptozotocin-induced Alzheimer rat model. Yonsei Med J, 2014, 55(3): 689-699

[31] KimJH, YenariMA, GiffardRG, et al.. Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury. Exp Neurol, 2004, 189(1): 122-130

[32] ZhuMY, PiletzJE, HalarisA, et al.. Effect of agmatine against cell death induced by NMDA and glutamate in neurons and PC12 cells. Cell Mol Neurobiol, 2003, 23(4–5): 865-872

[33] WangWP, IyoAH, Miguel-HidalgoJ, et al.. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res, 2006, 1084(1): 210-216

[34] ZdrojewiczZ, LachowskiM. The importance of putrescine in the human body. Postepy Hig Med Dosw (Online), 2014, 68: 393-403

[35] LiB, Lowe-PowerT, KuriharaS, et al.. Functional Identification of Putrescine C- and N-Hydroxylases. ACS Chem Biol, 2016, 11(10): 2782-2789

[36] Gomes-TrolinC, NygrenI, AquiloniusSM, et al.. Increased red blood cell polyamines in ALS and Parkinson’s disease. Exp Neurol, 2002, 177(2): 515-520

[37] JänneJ, AlhonenL, PietiläM, et al.. Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem, 2004, 271(5): 877-894

[38] ZahediK, HuttingerF, MorrisonR, et al.. Polyamine catabolism is enhanced after traumatic brain injury. J Neurotrauma, 2010, 27(3): 515-525

[39] de VeraN, CamónL, MartínezE. Cerebral distribution of polyamines in kainic acid-induced models of status epilepticus and ataxia in rats. Overproduction of putrescine and histological damage. Eur Neuropsychopharmacol, 2002, 12(5): 397-405

[40] MullerC, HerberthH, CosquerB, et al.. Structural and functional recovery elicited by combined putrescine and aminoguanidine treatment after aspirative lesion of the fimbria-fornix and overlying cortex in the adult rat. Eur J Neurosci, 2007, 25(7): 1949-1960

[41] KapfhamerD, McKennaJ, YoonCJ, et al.. Ornithine decarboxylase, the rate-limiting enzyme of polyamine synthesis, modifies brain pathology in a mouse model of tuberous sclerosis complex. Hum Mol Genet, 2020, 29(14): 2395-2407

[42] SatoM, ToyamaT, KimMS, et al.. Increased putrescine levels due to ODC1 overexpression prevents mitochondrial dysfunction-related apoptosis induced by methylmercury. Life Sci, 2020, 256: 118031

[43] MadeoF, EisenbergT, PietrocolaF, et al.. Spermidine in health and disease. Science, 2018, 359(6374): aan2788

[44] PekarT, WendzelA, FlakW, et al.. Spermidine in dementia: Relation to age and memory performance. Wien Klin Wochenschr, 2020, 132(1–2): 42-46

[45] HuangJ, ZhangH, ZhangJ, et al.. Spermidine Exhibits Protective Effects Against Traumatic Brain Injury. Cell Mol Neurobiol, 2020, 40(6): 927-937

[46] JamwalS, SinghS, KaurN, et al.. Protective Effect of Spermidine Against Excitotoxic Neuronal Death Induced by Quinolinic Acid in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism. Neurotox Res, 2015, 28(2): 171-184

[47] ZhuWW, XiaoF, TangYY, et al.. Spermidine prevents high glucose-induced senescence in HT-22 cells by upregulation of CB1 receptor. Clin Exp Pharmacol Physiol, 2018, 45(8): 832-840

[48] AbeK, ChidaN, NishiyamaN, et al.. Spermine promotes the survival of primary cultured brain neurons. Brain Res, 1993, 605(2): 322-326

[49] BhukelA, MadeoF, SigristSJ. Spermidine boosts autophagy to protect from synapse aging. Autophagy, 2017, 13(2): 444-445

[50] GuptaVK, ScheunemannL, EisenbergT, et al.. Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner. Nat Neurosci, 2013, 16(10): 1453-1460

[51] GargG, SinghS, SinghAK, et al.. Metformin Alleviates Altered Erythrocyte Redox Status During Aging in Rats. Rejuvenation Res, 2017, 20(1): 15-24

[52] SinghS, KumarR, GargG, et al.. Spermidine, a caloric restriction mimetic, provides neuroprotection against normal and D-galactose-induced oxidative stress and apoptosis through activation of autophagy in male rats during aging. Biogerontology, 2021, 22(1): 35-47

[53] KnottAB, Bossy-WetzelE. Impact of nitric oxide on metabolism in health and age-related disease. Diabetes Obes Metab, 2010, 12(Suppl202): 126-133

[54] WangY, XuE, MusichPR, et al.. Mitochondrial dysfunction in neurodegenerative diseases and the potential countermeasure. CNS Neurosci Ther, 2019, 25(7): 816-824

[55] RuiY, TiwariP, XieZ, et al.. Acute impairment of mitochondrial trafficking by beta-amyloid peptides in hippocampal neurons. J Neurosci, 2006, 26(41): 10480-10487

[56] RadiE, FormichiP, BattistiC, et al.. Apoptosis and oxidative stress in neurodegenerative diseases. J Alzheimers Dis, 2014, 42(Suppl3): S125-152

[57] Murray StewartT, DunstonTT, WosterPM, et al.. Polyamine catabolism and oxidative damage. J Biol Chem, 2018, 293(48): 18736-18745

[58] WuG, MorrisSMJr. Arginine metabolism: nitric oxide and beyond. Biochem J, 1998, 336: 1-17 Pt 1)(Pt 1)

[59] JiangH, KoubiD, ZhangL, et al.. Inhibitors of iNOS protects PC12 cells against the apoptosis induced by oxygen and glucose deprivation. Neurosci Lett, 2005, 375(1): 59-63

[60] GuoX, HaradaC, NamekataK, et al.. Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis. Invest Ophthalmol Vis Sci, 2011, 52(5): 2696-2703

[61] KeoghMJ, ChinneryPF. Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta, 2015, 1847(11): 1401-1411

[62] NittaT, IgarashiK, YamamotoN. Polyamine depletion induces apoptosis through mitochondria-mediated pathway. Exp Cell Res, 2002, 276(1): 120-128

[63] ZhangR, MaXN, LiuK, et al.. Exogenous spermine preserves mitochondrial bioenergetics via regulating Src kinase signaling in the spinal cord. Mol Med Rep, 2017, 16(3): 3619-3626

[64] LinMT, BealMF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006, 443(7113): 787-795

[65] KerrJS, AdriaanseBA, GreigNH, et al.. Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms. Trends Neurosci, 2017, 40(3): 151-166

[66] LiuR, LiX, MaH, et al.. Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy. Free Radic Biol Med, 2020, 161: 339-350

[67] BowieD. Polyamine-mediated channel block of ionotropic glutamate receptors and its regulation by auxiliary proteins. J Biol Chem, 2018, 293(48): 18789-18802

[68] HayashiT, HirshmanMF, FujiiN, et al.. Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes, 2000, 49(4): 527-531

[69] DasguptaB, MilbrandtJ. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci USA, 2007, 104(17): 7217-7222

[70] LiY, ChenC, YaoF, et al.. AMPK inhibits cardiac hypertrophy by promoting autophagy via mTORC1. Arch Biochem Biophys, 2014, 558: 79-86

[71] ZhaoM, LiXW, ChenZ, et al.. Neuro-Protective Role of Metformin in Patients with Acute Stroke and Type 2 Diabetes Mellitus via AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Pathway and Oxidative Stress. Med Sci Monit, 2019, 25: 2186-2194

[72] KimJ, FieselFC, BelmonteKC, et al.. miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1). Mol Neurodegener, 2016, 11(1): 55

[73] YangY, ChenS, ZhangY, et al.. Induction of autophagy by spermidine is neuroprotective via inhibition of caspase 3-mediated Beclin 1 cleavage. Cell Death Dis, 2017, 8(4): e2738

[74] SharmaS, KumarP, DeshmukhR. Neuroprotective potential of spermidine against rotenone induced Parkinson’s disease in rats. Neurochem Int, 2018, 116: 104-111

[75] UnokiM, NakamuraY. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene, 2001, 20(33): 4457-4465

[76] SarrafSA, RamanM, Guarani-PereiraV, et al.. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature, 2013, 496(7445): 372-376

[77] LazarouM, SliterDA, KaneLA, et al.. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature, 2015, 524(7565): 309-314

[78] Vives-BauzaC, ZhouC, HuangY, et al.. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci USA, 2010, 107(1): 378-383

[79] SchroederS, HoferSJ, ZimmermannA, et al.. Dietary spermidine improves cognitive function. Cell Rep, 2021, 35(2): 108985

[80] ZhouJJ, LuoY, ChenSR, et al.. LRRC8A-dependent volume-regulated anion channels contribute to ischemia-induced brain injury and glutamatergic input to hippocampal neurons. Exp Neurol, 2020, 332: 113391

[81] BarsoumMJ, YuanH, GerencserAA, et al.. Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J, 2006, 25(16): 3900-3911

[82] SalviM, ToninelloA. Effects of polyamines on mitochondrial Ca(2+) transport. Biochim Biophys Acta, 2004, 1661(2): 113-124

[83] NicholsCG, LeeSJ. Polyamines and potassium channels: A 25-year romance. J Biol Chem, 2018, 293(48): 18779-18788

[84] MattisonHA, BagalAA, MohammadiM, et al.. Evidence of calcium-permeable AMPA receptors in dendritic spines of CA1 pyramidal neurons. J Neurophysiol, 2014, 112(2): 263-275

[85] DharaM, MattaJA, LeiM, et al.. Polyamine regulation of ion channel assembly and implications for nicotinic acetylcholine receptor pharmacology. Nat Commun, 2020, 11(1): 2799

[86] FisherY, NemirovskyA, BaronR, et al.. T cells specifically targeted to amyloid plaques enhance plaque clearance in a mouse model of Alzheimer’s disease. PLoS One, 2010, 5(5): e10830

[87] MacianF. Autophagy in T Cell Function and Aging. Front Cell Dev Biol, 2019, 7: 213

[88] SodaK, KanoY, NakamuraT, et al.. Spermine, a natural polyamine, suppresses LFA-1 expression on human lymphocyte. J Immunol, 2005, 175(1): 237-245

[89] PeggAE. Functions of Polyamines in Mammals. J Biol Chem, 2016, 291(29): 14904-14912

[90] SastreM, GaleaE, FeinsteinD, et al.. Metabolism of agmatine in macrophages: modulation by lipopo-lysaccharide and inhibitory cytokines. Biochem J, 1998, 330: 1405-1409 Pt 3)

[91] OrellanaMS, JanaGA, FigueroaM, et al.. New Insights into the Determinants of Specificity in Human Type I Arginase: Generation of a Mutant That Is Only Active with Agmatine as Substrate. Int J Mol Sci, 2022, 23(12): 6438

[92] JenkinsonCP, GrodyWW, CederbaumSD. Comparative properties of arginases. Comp Biochem Physiol B Biochem Mol Biol, 1996, 114(1): 107-132

[93] CorneliusLP, RajuV, JulinA. Arginase Deficiency Presenting as Acute Encephalopathy. J Pediatr Neurosci, 2019, 14(3): 133-136

[94] CaiW, DaiX, ChenJ, et al.. STAT6/Arg1 promotes microglia/macrophage efferocytosis and inflammation resolution in stroke mice. JCI Insight, 2019, 4(20): e131355

[95] MadanS, KronB, JinZ, et al.. Arginase overexpression in neurons and its effect on traumatic brain injury. Mol Genet Metab, 2018, 125(1–2): 112-117

[96] BernsteinHG, DerstC, StichC, et al.. The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain. Amino Acids, 2011, 40(2): 453-465

[97] WeissT, BernardR, BernsteinHG, et al.. Agmatine modulates spontaneous activity in neurons of the rat medial habenular complex— a relevant mechanism in the pathophysiology and treatment of depression. Transl Psychiatry, 2018, 8(1): 201

[98] YılmazE, ŞekeroğluMR, YılmazE, et al.. Evaluation of plasma agmatine level and its metabolic pathway in patients with bipolar disorder during manic episode and remission period. Int J Psychiatry Clin Pract, 2019, 23(2): 128-133

[99] ZhuMY, IyoA, PiletzJE, et al.. Expression of human arginine decarboxylase, the biosynthetic enzyme for agmatine. Biochim Biophys Acta, 2004, 1670(2): 156-164

[100] IyoAH, ZhuMY, OrdwayGA, et al.. Expression of arginine decarboxylase in brain regions and neuronal cells. J Neurochem, 2006, 96(4): 1042-1050

[101] ParkYM, KimJH, LeeJE. Neural Stem Cells Overexpressing Arginine Decarboxylase Improve Functional Recovery from Spinal Cord Injury in a Mouse Model. Int J Mol Sci, 2022, 23(24): 15784

[102] BokaraKK, KwonKH, NhoY, et al.. Retroviral expression of arginine decarboxylase attenuates oxidative burden in mouse cortical neural stem cells. Stem Cells Dev, 2011, 20(3): 527-537

[103] ZhuMY, WangWP, HuangJ, et al.. Repeated immobilization stress alters rat hippocampal and prefrontal cortical morphology in parallel with endogenous agmatine and arginine decarboxylase levels. Neurochem Int, 2008, 53(6–8): 346-354

[104] LangeI, GeertsD, FeithDJ, et al.. Novel interaction of ornithine decarboxylase with sepiapterin reductase regulates neuroblastoma cell proliferation. J Mol Biol, 2014, 426(2): 332-346

[105] JacksonLK, GoldsmithEJ, PhillipsMA. X-ray structure determination of Trypanosoma brucei ornithine decarboxylase bound to D-ornithine and to G418: insights into substrate binding and ODC conformational flexibility. J Biol Chem, 2003, 278(24): 22037-22043

[106] NilssonT, MalkiewiczK, GabrielssonM, et al.. Antibody-bound amyloid precursor protein upregulates ornithine decarboxylase expression. Biochem Biophys Res Commun, 2006, 341(4): 1294-1299

[107] MäkitieLT, KanervaK, PolvikoskiT, et al.. Brain neurons express ornithine decarboxylase-activating antizyme inhibitor 2 with accumulation in Alzheimer’s disease. Brain Pathol, 2010, 20(3): 571-580

[108] PendevilleH, CarpinoN, MarineJC, et al.. The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol Cell Biol, 2001, 21(19): 6549-6558

[109] NishimuraK, NakatsuF, KashiwagiK, et al.. Essential role of S-adenosylmethionine decarboxylase in mouse embryonic development. Genes Cells, 2002, 7(1): 41-47

[110] ZhangD, ZhaoT, AngHS, et al.. AMD1 is essential for ESC self-renewal and is translationally down-regulated on differentiation to neural precursor cells. Genes Dev, 2012, 26(5): 461-473

[111] MahajanUV, VarmaVR, GriswoldME, et al.. Correction: Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study. PLoS Med, 2020, 17(10): e1003439

[112] Zabala-LetonaA, Arruabarrena-AristorenaA, Martín-MartínN, et al.. mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature, 2017, 547(7661): 109-113

[113] ToninelloA, SalviM, MondoviB. Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem, 2004, 11(17): 2349-2374

[114] ZhuX, ShouY, JiX, et al.. S-adenosylmethionine decarboxylase 1 and its related spermidine synthesis mediate PM(2.5) exposure-induced neuronal apoptosis. Ecotoxicol Environ Saf, 2021, 224: 112678

[115] BewleyMC, GrazianoV, JiangJ, et al.. Structures of wild-type and mutant human spermidine/spermine N1-acetyltransferase, a potential therapeutic drug target. Proc Natl Acad Sci USA, 2006, 103(7): 2063-2068

[116] CaseroRA, PeggAE. Polyamine catabolism and disease. Biochem J, 2009, 421(3): 323-338

[117] RayRM, BhattacharyaS, BavariaMN, et al.. Spermidine, a sensor for antizyme 1 expression regulates intracellular polyamine homeostasis. Amino Acids, 2014, 46(8): 2005-2013

[118] Nagesh BabuG, SailorKA, SunD, et al.. Spermidine/spermine N1-acetyl transferase activity in rat brain following transient focal cerebral ischemia and reperfusion. Neurosci Lett, 2001, 300(1): 17-20

[119] HanL, XuC, GuoY, et al.. Polyamine metabolism in rat myocardial ischemia-reperfusion injury. Int J Cardiol, 2009, 132(1): 142-144

[120] LiuJH, WangTW, LinYY, et al.. Acrolein is involved in ischemic stroke-induced neurotoxicity through spermidine/spermine-N1-acetyltransferase activation. Exp Neurol, 2020, 323: 113066

[121] KaasinenK, KoistinahoJ, AlhonenL, et al.. Overexpression of spermidine/spermine N-acetyltransferase in transgenic mice protects the animals from kainate-induced toxicity. Eur J Neurosci, 2000, 12(2): 540-548

[122] SeilerN. Catabolism of polyamines. Amino Acids, 2004, 26(3): 217-233

[123] CervelliM, AmendolaR, PolticelliF, et al.. Spermine oxidase: ten years after. Amino Acids, 2012, 42(2–3): 441-450

[124] CaponeC, CervelliM, AngelucciE, et al.. A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity. Free Radic Biol Med, 2013, 63: 99-107

[125] WeigerTM, HermannA. Cell proliferation, potassium channels, polyamines and their interactions: a mini review. Amino Acids, 2014, 46(3): 681-688

[126] PichavaramP, PalaniCD, PatelC, et al.. Targeting Polyamine Oxidase to Prevent Excitotoxicity-Induced Retinal Neurodegeneration. Front Neurosci, 2018, 12: 956

[127] WoodPL, KhanMA, MoskalJR, et al.. Aldehyde load in ischemia-reperfusion brain injury: neuroprotection by neutralization of reactive aldehydes with phenelzine. Brain Res, 2006, 1122(1): 184-190