{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:14:02Z","timestamp":1791688442726,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["SG-2018-12367839"],"award-info":[{"award-number":["SG-2018-12367839"]}]},{"name":"Italian Ministry of Health","award":["GGP20011"],"award-info":[{"award-number":["GGP20011"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mutations in the receptor expression-enhancing protein 1 gene (REEP1) are associated with hereditary spastic paraplegia type 31 (SPG31), a neurological disorder characterized by length-dependent degeneration of upper motor neuron axons. Mitochondrial dysfunctions have been observed in patients harboring pathogenic variants in REEP1, suggesting a key role of bioenergetics in disease-related manifestations. Nevertheless, the regulation of mitochondrial function in SPG31 remains unclear. To elucidate the pathophysiology underlying REEP1 deficiency, we analyzed in vitro the impact of two different mutations on mitochondrial metabolism. Together with mitochondrial morphology abnormalities, loss-of-REEP1 expression highlighted a reduced ATP production with increased susceptibility to oxidative stress. Furthermore, to translate these findings from in vitro to preclinical models, we knocked down REEP1 in zebrafish. Zebrafish larvae showed a significant defect in motor axon outgrowth leading to motor impairment, mitochondrial dysfunction, and reactive oxygen species accumulation. Protective antioxidant agents such as resveratrol rescued free radical overproduction and ameliorated the SPG31 phenotype both in vitro and in vivo. Together, our findings offer new opportunities to counteract neurodegeneration in SPG31.<\/jats:p>","DOI":"10.3390\/ijms24043527","type":"journal-article","created":{"date-parts":[[2023,2,10]],"date-time":"2023-02-10T02:56:13Z","timestamp":1675997773000},"page":"3527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Converging Role for REEP1\/SPG31 in Oxidative Stress"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-635X","authenticated-orcid":false,"given":"Valentina","family":"Naef","sequence":"first","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Meschini","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tessa","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-6878","authenticated-orcid":false,"given":"Federica","family":"Morani","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Corsinovi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2089-7412","authenticated-orcid":false,"given":"Asahi","family":"Ogi","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-0702","authenticated-orcid":false,"given":"Maria","family":"Marchese","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6777-0208","authenticated-orcid":false,"given":"Michela","family":"Ori","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M.","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-8253","authenticated-orcid":false,"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.expneurol.2014.06.011","article-title":"Hereditary spastic paraplegia: Clinical-genetic characteristics and evolving molecular mechanisms","volume":"261","author":"Lombardi","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1146\/annurev-neuro-062111-150400","article-title":"Cellular pathways of hereditary spastic paraplegia","volume":"35","author":"Blackstone","year":"2012","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00401-013-1115-8","article-title":"Hereditary spastic paraplegia: Clinico-pathological features and emerging molecular mechanisms","volume":"126","author":"Fink","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1093\/brain\/awn026","article-title":"REEP1 mutation spectrum and genotype\/phenotype correlation in hereditary spastic paraplegia type 31","volume":"131","author":"Beetz","year":"2008","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.1172\/JCI65665","article-title":"A spastic paraplegia mouse model reveals REEP1-dependent ER shaping","volume":"123","author":"Beetz","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/humu.21542","article-title":"REEP1 mutations in SPG31: Frequency, mutational spectrum, and potential association with mitochondrial morpho-functional dysfunction","volume":"32","author":"Goizet","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4134","DOI":"10.1172\/JCI72324","article-title":"REEPing the benefits of an animal model of hereditary spastic paraplegia","volume":"123","author":"Deutch","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/j.1468-1331.2010.03102.x","article-title":"Clinical and genetic findings in a series of Italian children with pure hereditary spastic paraplegia","volume":"18","author":"Battini","year":"2011","journal-title":"Eur. J. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/humu.22521","article-title":"Functional Mutation Analysis Provides Evidence for a Role of REEP1 in Lipid Droplet Biology","volume":"35","author":"Falk","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1002\/ana.24488","article-title":"Hereditary spastic paraplegia-linked REEP1 modulates endoplasmic reticulum\/mitochondria contacts","volume":"78","author":"Lim","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_11","first-page":"674","article-title":"Mitochondrial morphology and cellular distribution are altered in SPG31 patients and are linked to DRP1 hyperphosphorylation","volume":"26","author":"Lavie","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nature07534","article-title":"Mitofusin 2 tethers endoplasmic reticulum to mitochondria","volume":"456","author":"Scorrano","year":"2008","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1126\/science.1207385","article-title":"ER Tubules Mark Sites of Mitochondrial Division","volume":"334","author":"Friedman","year":"2011","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/embor.2010.115","article-title":"Mitochondrial shape changes: Orchestrating cell pathophysiology","volume":"11","author":"Campello","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0960-8966(01)00214-0","article-title":"Respiratory chain defects in hereditary spastic paraplegias","volume":"11","author":"Piemonte","year":"2001","journal-title":"Neuromuscul. Disord."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1212\/WNL.56.4.467","article-title":"Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigrees in northeast England","volume":"56","author":"McDermott","year":"2001","journal-title":"Neurology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1086\/339935","article-title":"Hereditary Spastic Paraplegia SPG13 Is Associated with a Mutation in the Gene Encoding the Mitochondrial Chaperonin Hsp60","volume":"70","author":"Hansen","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/ana.10757","article-title":"Hereditary spastic paraparesis: Disrupted intracellular transport associated with spastin mutation","volume":"54","author":"McDermott","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1093\/hmg\/ddl431","article-title":"A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition","volume":"15","author":"Tarrade","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1083\/jcb.200304112","article-title":"Loss of m-AAA protease in mitochondria causes complex I deficiency and increased sensitivity to oxidative stress in hereditary spastic paraplegia","volume":"163","author":"Atorino","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.braindev.2008.12.014","article-title":"Is oxidative damage in operation in patients with hereditary spastic paraparesis?","volume":"32","year":"2010","journal-title":"Brain Dev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1002\/2211-5463.13209","article-title":"Analogs of imine resveratrol alleviate oxidative stress-induced neurotoxicity in PC12 cells via activation of Nrf2","volume":"11","author":"Zhang","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.3389\/fnins.2019.01311","article-title":"Swimming in Deep Water: Zebrafish Modeling of Complicated Forms of Hereditary Spastic Paraplegia and Spastic Ataxia","volume":"13","author":"Naef","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fichi, G., Naef, V., Barca, A., Longo, G., Fronte, B., Verri, T., Santorelli, F.M., Marchese, M., and Petruzzella, V. (2019). Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102409"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/acn3.51018","article-title":"Loss of ap4s1 in zebrafish leads to neurodevelopmental defects resembling spastic paraplegia 52","volume":"7","author":"Tessa","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1007\/s00415-021-10509-6","article-title":"New pathogenic variants in COQ4 cause ataxia and neurodevelopmental disorder without detectable CoQ10 deficiency in muscle or skin fibroblasts","volume":"268","author":"Mero","year":"2021","journal-title":"J. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"590057","DOI":"10.3389\/fvets.2020.590057","article-title":"Social Preference Tests in Zebrafish: A Systematic Review","volume":"7","author":"Ogi","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.reprotox.2011.06.121","article-title":"Zebrafish embryos as an alternative to animal experiments\u2014A commentary on the definition of the onset of protected life stages in animal welfare regulations","volume":"33","author":"Scholz","year":"2012","journal-title":"Reprod. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s10048-008-0163-z","article-title":"New pedigrees and novel mutation expand the phenotype of REEP1-associated hereditary spastic paraplegia (HSP)","volume":"10","author":"Hewamadduma","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1074\/jbc.M807321200","article-title":"Respiratory complex I dysfunction due to mitochondrial DNA mutations shifts the voltage threshold for opening of the permeability transition pore toward resting levels","volume":"284","author":"Porcelli","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1056\/NEJMoa064436","article-title":"A Lethal Defect of Mitochondrial and Peroxisomal Fission","volume":"356","author":"Waterham","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8122","DOI":"10.1038\/s41598-018-26578-z","article-title":"Insight into the fission mechanism by quantitative characterization of Drp1 protein distribution in the living cell","volume":"8","author":"Michalska","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"15803","DOI":"10.1073\/pnas.0808249105","article-title":"Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria","volume":"105","author":"Cereghetti","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1212\/NXG.0000000000000032","article-title":"Recessive REEP1 mutation is associated with congenital axonal neuropathy and diaphragmatic palsy","volume":"1","author":"Schottmann","year":"2015","journal-title":"Neurol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.molmed.2006.04.002","article-title":"Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia","volume":"12","author":"Rugarli","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1749-6632.2010.05629.x","article-title":"Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1","volume":"1201","author":"Chang","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_37","first-page":"5111","article-title":"Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation","volume":"25","author":"Malone","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1038\/cdd.2012.18","article-title":"Inhibition of Drp1 provides neuroprotection in vitro and in vivo","volume":"19","author":"Grohm","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)81203-9","article-title":"Spastic paraplegia and OXPHOS impairment caused by mutations in paraplegin, a nuclear-encoded mitochondrial metalloprotease","volume":"93","author":"Casari","year":"1998","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/brain\/awq007","article-title":"Multi-system neurological disease is common in patients with OPA1 mutations","volume":"133","author":"Griffiths","year":"2010","journal-title":"Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jns.2015.05.033","article-title":"MFN2-related neuropathies: Clinical features, molecular pathogenesis and therapeutic perspectives","volume":"356","author":"Stuppia","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"bio054296","DOI":"10.1242\/bio.054296","article-title":"Inhibition of ER stress improves progressive motor deficits in a REEP1-null mouse model of hereditary spastic paraplegia","volume":"9","author":"Wang","year":"2020","journal-title":"Biol. Open"},{"key":"ref_43","first-page":"2003","article-title":"Oxidative stress, mitochondrial damage and neurodegenerative diseases","volume":"8","author":"Guo","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.brainres.2012.03.010","article-title":"Seung-YongYoon Increased phosphorylation of dynamin-related protein 1 and mitochondrial fission in okadaic acid-treated neurons","volume":"1454","author":"Cho","year":"2012","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/sj.emboj.7601963","article-title":"Fission and selective fusion govern mitochondrial segregation and elimination by autophagy","volume":"27","author":"Twig","year":"2008","journal-title":"EMBO J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1167\/iovs.07-0880","article-title":"Protection against oxidant-induced apoptosis by exogenous glutathione in leber hereditary optic neuropathy cybrids","volume":"49","author":"Ghelli","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/YCO.0000000000000605","article-title":"The role of diet in preventing and reducing cognitive decline","volume":"33","author":"Angeloni","year":"2020","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/BST20170501","article-title":"Mitochondrial abnormalities in Parkinson\u2019s disease and Alzheimer\u2019s disease: Can mitochondria be targeted therapeutically?","volume":"46","author":"Macdonald","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112164","DOI":"10.1016\/j.biopha.2021.112164","article-title":"Resveratrol (RV): A pharmacological review and call for further research","volume":"143","author":"Zhang","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Salehi, B., Mishra, A.P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P.V.T., Martins, N., and Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines, 6.","DOI":"10.3390\/biomedicines6030091"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Signorile, A., Ferretta, A., Pacelli, C., Capitanio, N., Tanzarella, P., Matrella, M.L., Valletti, A., De Rasmo, D., and Cocco, T. (2021). Resveratrol Treatment in Human Parkin-Mutant Fibroblasts Modulates cAMP and Calcium Homeostasis Regulating the Expression of Mitochondria-Associated Membranes Resident Proteins. Biomolecules, 11.","DOI":"10.3390\/biom11101511"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2010.03.024","article-title":"Proneural gene-linked neurogenesis in zebrafish cerebellum","volume":"343","author":"Kani","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Naef, V., Marchese, M., Ogi, A., Fichi, G., Galatolo, D., Licitra, R., Doccini, S., Verri, T., Argenton, F., and Morani, F. (2021). Efficient Neuroprotective Rescue of Sacsin-Related Disease Phenotypes in Zebrafish. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168401"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"C881","DOI":"10.1152\/ajpcell.00104.2005","article-title":"Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency","volume":"289","author":"Koopman","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13843","DOI":"10.1074\/jbc.M808515200","article-title":"Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission","volume":"284","author":"Dagda","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1007\/s00415-015-7911-4","article-title":"Powerhouse failure and oxidative damage in autosomal recessive spastic ataxia of Charlevoix-Saguenay","volume":"262","author":"Criscuolo","year":"2015","journal-title":"J. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41420-020-0250-y","article-title":"Proteomic and functional analyses in disease models reveal CLN5 protein involvement in mitochondrial dysfunction","volume":"6","author":"Doccini","year":"2020","journal-title":"Cell Death Discov."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Doccini, S., Marchese, M., Morani, F., Gammaldi, N., Mero, S., Pezzini, F., Soliymani, R., Santi, M., Signore, G., and Ogi, A. (2022). Lysosomal Proteomics Links Disturbances in Lipid Homeostasis and Sphingolipid Metabolism to CLN5 Disease. Cells, 11.","DOI":"10.3390\/cells11111840"},{"key":"ref_59","unstructured":"Kam, Y., Rogers, G.W., Jastromb, N., and Dranka, B.P. (2023, February 06). Methods and strategies for normalizing XF metabolic data to cellular parameters. Available online: https:\/\/www.agilent.com\/cs\/library\/technicaloverviews\/public\/Methods_and_Strategies_for_Normalizing_Tech_Overview_022118.pdf."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Brogi, L., Marchese, M., Cellerino, A., Licitra, R., Naef, V., Mero, S., Bibbiani, C., and Fronte, B. (2021). \u03b2-Glucans as Dietary Supplement to Improve Locomotion and Mitochondrial Respiration in a Model of Duchenne Muscular Dystrophy. Nutrients, 13.","DOI":"10.3390\/nu13051619"},{"key":"ref_62","first-page":"S1","article-title":"The 3Rs in research: A contemporary approach to replacement, reduction and refinement","volume":"120","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bbrc.2016.06.033","article-title":"Dolichol-phosphate mannose synthase depletion in zebrafish leads to dystrophic muscle with hypoglycosylated \u03b1-dystroglycan","volume":"477","author":"Marchese","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Della Vecchia, S., Ogi, A., Licitra, R., Abramo, F., Nardi, G., Mero, S., Landi, S., Battini, R., Sicca, F., and Ratto, G.M. (2022). Trehalose Treatment in Zebrafish Model of Lafora Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126874"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"549533","DOI":"10.3389\/fcell.2020.549533","article-title":"The Stemness Gene Mex3A Is a Key Regulator of Neuroblast Proliferation during Neurogenesis","volume":"8","author":"Naef","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nprot.2007.514","article-title":"High-resolution in situ hybridization to whole-mount zebrafish embryos","volume":"3","author":"Thisse","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"104757","DOI":"10.1016\/j.nbd.2020.104757","article-title":"Distal motor neuropathy associated with novel EMILIN1 mutation","volume":"137","author":"Iacomino","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Giordo, R., Nasrallah, G.K., Al-Jamal, O., Paliogiannis, P., and Pintus, G. (2020). Resveratrol Inhibits Oxidative Stress and Prevents Mitochondrial Damage Induced by Zinc Oxide Nanoparticles in Zebrafish (Danio rerio). Int. J. Mol. 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