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Hirakawa T, Taniuchi M, Iguchi Y, Bogahawaththa S, Yoshitake K, Werellagama S, Uemura T, Tsujita T. NF-E2-related factor 1 suppresses the expression of a spermine oxidase and the production of highly reactive acrolein. Sci Rep 2025; 15:12405. [PMID: 40258928 PMCID: PMC12012012 DOI: 10.1038/s41598-025-96388-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Accepted: 03/27/2025] [Indexed: 04/23/2025] Open
Abstract
Polyamines (putrescine, spermidine, and spermine) are among the most abundant intracellular small molecular metabolites, with concentrations at the mM level. The ratios of these three molecules remain constant under physiological conditions. Stress (i.e. polyamine overload, oxidative stress, aging, infection, etc.) triggers the catabolic conversion of spermine to spermidine, ultimately yielding acrolein and hydrogen peroxide. The potential of acrolein to induce DNA damage and protein denaturation is 1,000 times greater than that of reactive oxygen species. We have shown that these polyamine metabolic pathways also involve the nuclear factor erythroid-2-related factor 1 (NRF1) transcription factor. In our chemically-inducible, liver-specific Nrf1-knockout mice, the polyamine catabolic pathway dominated the anabolic pathway, producing free acrolein and accumulating acrolein-conjugated proteins in vivo. This metabolic feature implicates SMOX as an important causative enzyme. Chromatin immunoprecipitation and reporter assays confirmed that NRF1 directly suppressed Smox expression. This effect was also observed in vitro. Ectopic overexpression of SMOX increased the accumulation of free acrolein and acrolein-conjugated proteins. SMOX knockdown reversed the accumulation of free acrolein and acrolein-conjugated proteins. Our results show that NRF1 typically suppresses Smox expression when NRF1 is downregulated, SMOX is upregulated, and polyamine metabolic pathways are altered, producing low molecular weight polyamines and acrolein.
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Affiliation(s)
- Tomoaki Hirakawa
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
| | - Megumi Taniuchi
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
| | - Yoko Iguchi
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
| | - Sudarma Bogahawaththa
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan
| | - Kiko Yoshitake
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
| | - Shanika Werellagama
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan
| | - Takeshi Uemura
- Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, Saitama, Japan
| | - Tadayuki Tsujita
- Laboratory of Biochemistry, Faculty of Agriculture, Saga University, Saga, Japan.
- The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan.
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Uemura T, Matsunaga M, Yokota Y, Takao K, Furuchi T. Inhibition of Polyamine Catabolism Reduces Cellular Senescence. Int J Mol Sci 2023; 24:13397. [PMID: 37686212 PMCID: PMC10488189 DOI: 10.3390/ijms241713397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/25/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine, spermidine, and spermine) are essential for cell growth and function. Age-related reductions in polyamine levels have been shown to be associated with reduced cognitive and physical functions. We have previously found that the expression of spermine oxidase (SMOX) increases with age; however, the relationship between SMOX expression and cellular senescence remains unclear. Therefore, we investigated the relationship between increased SMOX expression and cellular senescence using human-liver-derived HepG2 cells. Intracellular spermine levels decreased and spermidine levels increased with the serial passaging of cells (aged cells), and aged cells showed increased expression of SMOX. The levels of acrolein-conjugated protein, which is produced during spermine degradation, also increases. Senescence-associated β-gal activity was increased in aged cells, and the increase was suppressed by MDL72527, an inhibitor of acetylpolyamine oxidase (AcPAO) and SMOX, both of which are enzymes that catalyze polyamine degradation. DNA damage accumulated in aged cells and MDL72527 reduced DNA damage. These results suggest that the SMOX-mediated degradation of spermine plays an important role in cellular senescence. Our results demonstrate that cellular senescence can be controlled by inhibiting spermine degradation using a polyamine-catabolizing enzyme inhibitor.
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Affiliation(s)
- Takeshi Uemura
- Faculty of Pharmacy and Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado 350-0295, Saitama, Japan (K.T.); (T.F.)
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Treatment with MDL 72527 Ameliorated Clinical Symptoms, Retinal Ganglion Cell Loss, Optic Nerve Inflammation, and Improved Visual Acuity in an Experimental Model of Multiple Sclerosis. Cells 2022; 11:cells11244100. [PMID: 36552864 PMCID: PMC9776605 DOI: 10.3390/cells11244100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 12/24/2022] Open
Abstract
Multiple Sclerosis (MS) is a highly disabling neurological disease characterized by inflammation, neuronal damage, and demyelination. Vision impairment is one of the major clinical features of MS. Previous studies from our lab have shown that MDL 72527, a pharmacological inhibitor of spermine oxidase (SMOX), is protective against neurodegeneration and inflammation in the models of diabetic retinopathy and excitotoxicity. In the present study, utilizing the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined the impact of SMOX blockade on retinal neurodegeneration and optic nerve inflammation. The increased expression of SMOX observed in EAE retinas was associated with a significant loss of retinal ganglion cells, degeneration of synaptic contacts, and reduced visual acuity. MDL 72527-treated mice exhibited markedly reduced motor deficits, improved neuronal survival, the preservation of synapses, and improved visual acuity compared to the vehicle-treated group. The EAE-induced increase in macrophage/microglia was markedly reduced by SMOX inhibition. Upregulated acrolein conjugates in the EAE retina were decreased through MDL 72527 treatment. Mechanistically, the EAE-induced ERK-STAT3 signaling was blunted by SMOX inhibition. In conclusion, our studies demonstrate the potential benefits of targeting SMOX to treat MS-mediated neuroinflammation and vision loss.
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Bernstein HG, Keilhoff G, Laube G, Dobrowolny H, Steiner J. Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy. World J Psychiatry 2021; 11:1177-1190. [PMID: 35070769 PMCID: PMC8717027 DOI: 10.5498/wjp.v11.i12.1177] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/30/2021] [Accepted: 11/25/2021] [Indexed: 02/06/2023] Open
Abstract
Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.
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Affiliation(s)
- Hans-Gert Bernstein
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Gerburg Keilhoff
- Institute of Biochemistry and Cell Biology, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Gregor Laube
- Department of Anatomy, Charite, Berlin D-10117, Germany
| | - Henrik Dobrowolny
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
| | - Johann Steiner
- Department of Psychiatry, University of Magdeburg, Magdeburg D-39116, Saxony-Anhalt, Germany
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Nakanishi S, Cleveland JL. Polyamine Homeostasis in Development and Disease. MEDICAL SCIENCES (BASEL, SWITZERLAND) 2021; 9:medsci9020028. [PMID: 34068137 PMCID: PMC8162569 DOI: 10.3390/medsci9020028] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/02/2021] [Accepted: 05/06/2021] [Indexed: 12/12/2022]
Abstract
Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.
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Correlation of polyamines, acrolein-conjugated lysine and polyamine metabolic enzyme levels with age in human liver. Heliyon 2020; 6:e05031. [PMID: 32995657 PMCID: PMC7512001 DOI: 10.1016/j.heliyon.2020.e05031] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/21/2020] [Accepted: 09/18/2020] [Indexed: 12/13/2022] Open
Abstract
The polyamines spermidine, spermine and putrescine are essential for normal cellular functions. The contents of polyamines in tissue decreased in aged mice compared to young mice. In this study, the polyamine contents and their metabolic byproduct acrolein-conjugated lysine (Nε-(3-formyl-3,4-dehydropiperidino)-lysine, FDP-Lys) in human liver tissue were measured and analyzed the correlation with age of the subjects. The putrescine and FDP-Lys levels were significantly increased with age. On the other hand, spermine level was decreased with age. Spermidine did not significantly correlate with age. The relative amount of spermine oxidase (SMOX) significantly correlated with the age of subjects whereas ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AMD1) significantly reduced by the age. Our results suggested that an increase in oxidation and reduction in polyamine synthesis may cause the change of polyamine profile in the elderly.
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Sun L, Yang J, Qin Y, Wang Y, Wu H, Zhou Y, Cao C. Discovery and antitumor evaluation of novel inhibitors of spermine oxidase. J Enzyme Inhib Med Chem 2019; 34:1140-1151. [PMID: 31159606 PMCID: PMC6567099 DOI: 10.1080/14756366.2019.1621863] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Revised: 03/26/2019] [Accepted: 05/16/2019] [Indexed: 12/22/2022] Open
Abstract
Increasing knowledge of the relationship between cancer and dysregulated polyamine catabolism suggests interfering with aberrant polyamine metabolism for anticancer therapy that will have considerable clinical promise. SMO (spermine oxidase) plays an essential role in regulating the polyamines homeostasis. Therefore, development of SMO inhibitors has increasingly attracted much attention. Previously, we successfully purified and characterised SMO. Here, we presented an in silico drug discovery pipeline by combining pharmacophore modelling and molecular docking for the virtual screening of SMO inhibitors. In vitro evaluation showed that N-(3-{[3-(dimethylamino)propyl]amino}propyl)-8-quinolinecarboxamide (SI-4650) inhibited SMO enzyme activity, increased substrate spermine content and reduced product spermidine content, indicating that SI-4650 can interfere with polyamine metabolism. Furthermore, SI-4650 treatment suppressed cell proliferation and migration. Mechanistically, SI-4650 caused cell cycle arrest, induced cell apoptosis, and promoted autophagy. These results demonstrated the properties of interfering with polyamine metabolism of SI-4650 as a SMO inhibitor and the potential for cancer treatment.
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Affiliation(s)
- Lidan Sun
- College of Chemical Engineering and Material Science, Quanzhou Normal University, Quanzhou, China
| | - Jianlin Yang
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
| | - Yu Qin
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
| | - Yanlin Wang
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
| | - Hongyan Wu
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
| | - You Zhou
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
| | - Chunyu Cao
- Hubei Key Laboratory of Tumour Microenvironment and Immunotherapy, China Three Gorges University Medical College, Yichang, China
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Comparative Analysis of MicroRNA and mRNA Profiles of Sperm with Different Freeze Tolerance Capacities in Boar ( Sus scrofa) and Giant Panda ( Ailuropoda melanoleuca). Biomolecules 2019; 9:biom9090432. [PMID: 31480517 PMCID: PMC6769438 DOI: 10.3390/biom9090432] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 08/29/2019] [Accepted: 08/29/2019] [Indexed: 12/19/2022] Open
Abstract
Post-thawed sperm quality parameters vary across different species after cryopreservation. To date, the molecular mechanism of sperm cryoinjury, freeze-tolerance and other influential factors are largely unknown. In this study, significantly dysregulated microRNAs (miRNAs) and mRNAs in boar and giant panda sperm with different cryo-resistance capacity were evaluated. From the result of miRNA profile of fresh and frozen-thawed giant panda sperm, a total of 899 mature, novel miRNAs were identified, and 284 miRNAs were found to be significantly dysregulated (195 up-regulated and 89 down-regulated). Combined analysis of miRNA profiling of giant panda sperm and our previously published data on boar sperm, 46, 21 and 4 differentially expressed (DE) mRNAs in boar sperm were believed to be related to apoptosis, glycolysis and oxidative phosphorylation, respectively. Meanwhile, 87, 17 and 7 DE mRNAs in giant panda were associated with apoptosis, glycolysis and oxidative phosphorylation, respectively. Gene ontology (GO) analysis of the targets of DE miRNAs showed that they were mainly distributed on membrane related pathway in giant panda sperm, while cell components and cell processes were tied to the targets of DE miRNAs in boar sperm. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DE mRNAs indicated that most of these DE mRNAs were distributed in membrane signal transduction-related pathways in giant panda sperm, while those in boar sperm were mainly distributed in the cytokine-cytokine receptor interaction pathway and inflammatory related pathways. In conclusion, although the different freezing extenders and programs were used, the DE miRNAs and mRNAs involved in apoptosis, energy metabolism, olfactory transduction pathway, inflammatory response and cytokine-cytokine interactions, could be the possible molecular mechanism of sperm cryoinjury and freeze tolerance.
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Inhibition of dendritic spine extension through acrolein conjugation with α-, β-tubulin proteins. Int J Biochem Cell Biol 2019; 113:58-66. [PMID: 31150838 DOI: 10.1016/j.biocel.2019.05.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 05/24/2019] [Accepted: 05/27/2019] [Indexed: 11/23/2022]
Abstract
We have recently found that conjugation of acrolein with a 50 kDa protein(s) is strongly associated with tissue damage during brain infarction. In the current study, the identity and function of the 50 kDa protein(s) conjugated with acrolein during brain infarction were investigated. The 50 kDa protein(s) conjugated with acrolein were identified as α- and β-tubulins. Ten cysteine residues in α- and β-tubulins (Cys25, 295, 347 and 376 in α-tubulin and Cys12, 129, 211, 239, 303 and 354 in β-tubulin) were mainly conjugated with acrolein. Since two cysteine residues of α-tubulin (Cys347 and 376) and four cysteine residues of β-tubulin (Cys12, 129, 239 and 354) were located at the interaction site of α- and β-tubulins, association between α- and β-tubulins to form microtubules was strongly inhibited by conjugation with acrolein. Accordingly, dendritic spine extension consisting of microtubules was greatly inhibited in acrolein-treated Neuro2a cells. The results strongly suggest that acrolein contributes to the functional losses in brain signaling through its conjugation with α- and β-tubulins.
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Ye Z, Zeng Z, Shen Y, Yang Q, Chen D, Chen Z, Shen S. ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma. Onco Targets Ther 2019; 12:4081-4092. [PMID: 31239700 PMCID: PMC6553997 DOI: 10.2147/ott.s198341] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 03/29/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose: Ornithine decarboxylase 1 (ODC1)–an oncogene involved in the biosynthesis of polyamines–is commonly upregulated and associated with poor prognosis in numerous cancers. However, the role and mechanism of ODC1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to investigate the role of ODC1 in HCC and clarify the latent molecular mechanisms. Material and methods: We used samples obtained from The Cancer Genome Atlas. The expression of ODC1 was also assessed in our additional HCC samples and HCC cell lines. The roles of ODC1 in HCC cell proliferation, migration and invasion in vitro were investigated using the cell-counting kit-8 assay, 5-ethynyl-2´-deoxyuridine assay, colony formation assay, flow cytometry, wound healing assay and transwell assay, respectively. The effect of ODC1 on HCC cell proliferation in vivo was investigated by constructing a xenotransplanted tumor model in nude mice. Quantitative real-time polymerase chain and western blotting were used to detect the expression levels of ODC1 in mimetic hypoxia, nutrient depleted, and acidotic microenvironment. The relationships between ODC1, the AKT/GSK3β/β-catenin pathway, and acidotic microenvironment were further investigated through western blotting, immunohistochemical staining, and immunofluorescence. Results: ODC1 was upregulated in HCC tissues and cell lines, and co-expressed with KI67 and PCNA (P<0.05). A decrease in the expression of ODC1 inhibits proliferation, migration, invasion, and induces cell cycle arrest in HCC cell lines in vitro, while suppressing HCC cell proliferation in vivo (P<0.05). Furthermore, the expression of ODC1 was increased in the mimetic acidotic microenvironment, while the interference with the expression of ODC1 reversed the effect of the acidotic microenvironment through regulation of AKT/GSK3β/β-catenin and related downstream proteins. Conclusion: ODC1 is an unfavorable gene in HCC patients,promoting HCC cell proliferation, migration and invasion via the AKT/GSK3β/β-catenin pathway and modulation of the acidotic microenvironment.
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Affiliation(s)
- Zi Ye
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China
| | - Zhirui Zeng
- Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Guiyang, Guizhou 550009, People's Republic of China.,Department of Physiology, School of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou 550009, People's Republic of China
| | - Yiyi Shen
- Department of Liver-Biliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People's Republic of China
| | - Qiang Yang
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China
| | - Duidui Chen
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China
| | - Zubing Chen
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China
| | - Shiqiang Shen
- Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China
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Cervelli M, Leonetti A, Duranti G, Sabatini S, Ceci R, Mariottini P. Skeletal Muscle Pathophysiology: The Emerging Role of Spermine Oxidase and Spermidine. Med Sci (Basel) 2018; 6:medsci6010014. [PMID: 29443878 PMCID: PMC5872171 DOI: 10.3390/medsci6010014] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/07/2018] [Accepted: 02/09/2018] [Indexed: 12/25/2022] Open
Abstract
Skeletal muscle comprises approximately 40% of the total body mass. Preserving muscle health and function is essential for the entire body in order to counteract chronic diseases such as type II diabetes, cardiovascular diseases, and cancer. Prolonged physical inactivity, particularly among the elderly, causes muscle atrophy, a pathological state with adverse outcomes such as poor quality of life, physical disability, and high mortality. In murine skeletal muscle C2C12 cells, increased expression of the spermine oxidase (SMOX) enzyme has been found during cell differentiation. Notably, SMOX overexpression increases muscle fiber size, while SMOX reduction was enough to induce muscle atrophy in multiple murine models. Of note, the SMOX reaction product spermidine appears to be involved in skeletal muscle atrophy/hypertrophy. It is effective in reactivating autophagy, ameliorating the myopathic defects of collagen VI-null mice. Moreover, spermidine treatment, if combined with exercise, can affect D-gal-induced aging-related skeletal muscle atrophy. This review hypothesizes a role for SMOX during skeletal muscle differentiation and outlines its role and that of spermidine in muscle atrophy. The identification of new molecular pathways involved in the maintenance of skeletal muscle health could be beneficial in developing novel therapeutic lead compounds to treat muscle atrophy.
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Affiliation(s)
- Manuela Cervelli
- Department of Science, Università degli Studi di Roma "Roma Tre", 00146 Rome, Italy.
| | - Alessia Leonetti
- Department of Science, Università degli Studi di Roma "Roma Tre", 00146 Rome, Italy.
| | - Guglielmo Duranti
- Department of of Movement Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Piazza Lauro De Bosis 15, 00135 Rome, Italy.
| | - Stefania Sabatini
- Department of of Movement Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Piazza Lauro De Bosis 15, 00135 Rome, Italy.
| | - Roberta Ceci
- Department of of Movement Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Università degli Studi di Roma "Foro Italico", Piazza Lauro De Bosis 15, 00135 Rome, Italy.
| | - Paolo Mariottini
- Department of Science, Università degli Studi di Roma "Roma Tre", 00146 Rome, Italy.
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