{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T22:29:51Z","timestamp":1773181791101,"version":"3.50.1"},"reference-count":62,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Padova","award":["SID 2019"],"award-info":[{"award-number":["SID 2019"]}]},{"name":"University of Padova","award":["PRIN2017XA5J5N"],"award-info":[{"award-number":["PRIN2017XA5J5N"]}]},{"name":"University of Padova","award":["CeBioND"],"award-info":[{"award-number":["CeBioND"]}]},{"name":"Italian Ministry of University and Scientific Research","award":["SID 2019"],"award-info":[{"award-number":["SID 2019"]}]},{"name":"Italian Ministry of University and Scientific Research","award":["PRIN2017XA5J5N"],"award-info":[{"award-number":["PRIN2017XA5J5N"]}]},{"name":"Italian Ministry of University and Scientific Research","award":["CeBioND"],"award-info":[{"award-number":["CeBioND"]}]},{"name":"EU Joint Programme in Neurodegenerative Disease (Grant CeBioND)","award":["SID 2019"],"award-info":[{"award-number":["SID 2019"]}]},{"name":"EU Joint Programme in Neurodegenerative Disease (Grant CeBioND)","award":["PRIN2017XA5J5N"],"award-info":[{"award-number":["PRIN2017XA5J5N"]}]},{"name":"EU Joint Programme in Neurodegenerative Disease (Grant CeBioND)","award":["CeBioND"],"award-info":[{"award-number":["CeBioND"]}]},{"name":"UNIPD Funds","award":["SID 2019"],"award-info":[{"award-number":["SID 2019"]}]},{"name":"UNIPD Funds","award":["PRIN2017XA5J5N"],"award-info":[{"award-number":["PRIN2017XA5J5N"]}]},{"name":"UNIPD Funds","award":["CeBioND"],"award-info":[{"award-number":["CeBioND"]}]},{"name":"Euro Bioimaging Project Roadmap\/ESFRI","award":["SID 2019"],"award-info":[{"award-number":["SID 2019"]}]},{"name":"Euro Bioimaging Project Roadmap\/ESFRI","award":["PRIN2017XA5J5N"],"award-info":[{"award-number":["PRIN2017XA5J5N"]}]},{"name":"Euro Bioimaging Project Roadmap\/ESFRI","award":["CeBioND"],"award-info":[{"award-number":["CeBioND"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in presenilin 2 (PS2) have been causally linked to the development of inherited Alzheimer\u2019s disease (AD). Besides its role as part of the \u03b3-secretase complex, mammalian PS2 is also involved, as an individual protein, in a growing number of cell processes, which result altered in AD. To gain more insight into PS2 (dys)functions, we have generated a presenilin2 (psen2) knockout zebrafish line. We found that the absence of the protein does not markedly influence Notch signaling at early developmental stages, suggesting a Psen2 dispensable role in the \u03b3-secretase-mediated Notch processing. Instead, loss of Psen2 induces an exaggerated locomotor response to stimulation in fish larvae, a reduced number of ER-mitochondria contacts in zebrafish neurons, and an increased basal autophagy. Moreover, the protein is involved in mitochondrial axonal transport, since its acute downregulation reduces in vivo organelle flux in zebrafish sensory neurons. Importantly, the expression of a human AD-linked mutant of the protein increases this vital process. Overall, our results confirm zebrafish as a good model organism for investigating PS2 functions in vivo, representing an alternative tool for the characterization of new AD-linked defective cell pathways and the testing of possible correcting drugs.<\/jats:p>","DOI":"10.3390\/cells12030376","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:43:29Z","timestamp":1674182609000},"page":"376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unraveling Presenilin 2 Functions in a Knockout Zebrafish Line to Shed Light into Alzheimer\u2019s Disease Pathogenesis"],"prefix":"10.3390","volume":"12","author":[{"given":"Lucia","family":"Barazzuol","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Cieri","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4898-4064","authenticated-orcid":false,"given":"Nicola","family":"Facchinello","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padua, Italy"},{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8901-1659","authenticated-orcid":false,"given":"Tito","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padua, Italy"},{"name":"Centro Studi per la Neurodegenerazione (CESNE), University of Padova, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-1282","authenticated-orcid":false,"given":"Philip","family":"Washbourne","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0803-8236","authenticated-orcid":false,"given":"Francesco","family":"Argenton","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-3265","authenticated-orcid":false,"given":"Paola","family":"Pizzo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35131 Padua, Italy"},{"name":"Neuroscience Institute, National Research Council (CNR), 35131 Padua, Italy"},{"name":"Centro Studi per la Neurodegenerazione (CESNE), University of Padova, 35131 Padua, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa1202753","article-title":"Clinical and Biomarker Changes in Dominantly Inherited Alzheimer\u2019s Disease","volume":"367","author":"Bateman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ncl.2017.01.005","article-title":"Early\u2013Onset Alzheimer Disease","volume":"35","author":"Mendez","year":"2017","journal-title":"Neurol. Clin"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"695808","DOI":"10.3389\/fnagi.2021.695808","article-title":"APP, PSEN1, and PSEN2 Variants in Alzheimer\u2019s Disease: Systematic Re\u2013evaluation According to ACMG Guidelines","volume":"13","author":"Xiao","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cell.2016.05.020","article-title":"Restricted Location of PSEN2\/gamma-Secretase Determines Substrate Specificity and Generates an Intracellular Abeta Pool","volume":"166","author":"Sannerud","year":"2016","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/2047-9158-2-15","article-title":"Biological function of Presenilin and its role in AD pathogenesis","volume":"2","author":"Zhang","year":"2013","journal-title":"Transl. Neurodegener."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.2353\/ajpath.2009.090219","article-title":"Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria","volume":"175","author":"Boldogh","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1073\/pnas.1100735108","article-title":"Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk","volume":"108","author":"Zampese","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1016\/j.celrep.2016.05.013","article-title":"Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2","volume":"15","author":"Filadi","year":"2016","journal-title":"Cell Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E2174","DOI":"10.1073\/pnas.1504880112","article-title":"Mitofusin 2 ablation increases endoplasmic reticulum\u2013mitochondria coupling","volume":"112","author":"Filadi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.nbd.2003.11.002","article-title":"The presenilin 2 M239I mutation associated with familial Alzheimer\u2019s disease reduces Ca2+ release from intracellular stores","volume":"15","author":"Zatti","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.nbd.2004.10.016","article-title":"Reduction of Ca2+ stores and capacitative Ca2+ entry is associated with the familial Alzheimer\u2019s disease presenilin-2 T122R mutation and anticipates the onset of dementia","volume":"18","author":"Giacomello","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.ceca.2006.03.002","article-title":"Presenilin mutations linked to familial Alzheimer\u2019s disease reduce endoplasmic reticulum and Golgi apparatus calcium levels","volume":"39","author":"Zatti","year":"2006","journal-title":"Cell Calcium"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1111\/j.1582-4934.2009.00755.x","article-title":"Presenilin-2 dampens intracellular Ca2+ stores by increasing Ca2+ leakage and reducing Ca2+ uptake","volume":"13","author":"Brunello","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.1474-9726.2012.00858.x","article-title":"Ca2+ dysregulation in neurons from transgenic mice expressing mutant presenilin 2","volume":"11","author":"Kipanyula","year":"2012","journal-title":"Aging Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ceca.2019.02.005","article-title":"Familial Alzheimer\u2019s disease-linked presenilin mutants and intracellular Ca(2+) handling: A single-organelle, FRET-based analysis","volume":"79","author":"Greotti","year":"2019","journal-title":"Cell Calcium"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1080\/15548627.2019.1596489","article-title":"PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca2+ homeostasis","volume":"15","author":"Fedeli","year":"2019","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.celrep.2020.01.060","article-title":"Defective Mitochondrial Pyruvate Flux Affects Cell Bioenergetics in Alzheimer\u2019s Disease-Related Models","volume":"30","author":"Rossi","year":"2020","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12924","DOI":"10.1111\/acel.12924","article-title":"Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer\u2019s disease neurons","volume":"18","author":"Theurey","year":"2019","journal-title":"Aging Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1007\/s00427-002-0269-5","article-title":"Identification of a second presenilin gene in zebrafish with similarity to the human Alzheimer\u2019s disease gene presenilin2","volume":"212","author":"Groth","year":"2002","journal-title":"Dev. Genes Evol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13602","DOI":"10.1021\/bi991453n","article-title":"Zebrafish (Danio rerio) presenilin promotes aberrant amyloid beta-peptide production and requires a critical aspartate residue for its function in amyloidogenesis","volume":"38","author":"Leimer","year":"1999","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/j.1471-4159.2006.03648.x","article-title":"Zebrafish lacking Alzheimer presenilin enhancer 2 (Pen-2) demonstrate excessive p53-dependent apoptosis and neuronal loss","volume":"96","author":"Campbell","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s00429-009-0237-1","article-title":"Transgenic zebrafish models of neurodegenerative diseases","volume":"214","author":"Sager","year":"2010","journal-title":"Anat. Embryol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/S0014-4827(03)00257-X","article-title":"Developmental control of Presenilin1 expression, endoproteolysis, and interaction in zebrafish embryos","volume":"289","author":"Nornes","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1093\/hmg\/ddm317","article-title":"Interference with splicing of Presenilin transcripts has potent dominant negative effects on Presenilin activity","volume":"17","author":"Nornes","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Jiang, H., Newman, M., and Lardelli, M. (2018). The zebrafish orthologue of familial Alzheimer\u2019s disease gene PRESENILIN 2 is required for normal adult melanotic skin pigmentation. PLoS ONE, 13.","DOI":"10.1101\/414144"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3233\/ADR-200279","article-title":"In-Frame and Frameshift Mutations in Zebrafish Presenilin 2 Affect Different Cellular Functions in Young Adult Brains","volume":"5","author":"Barthelson","year":"2021","journal-title":"J. Alzheimer\u2019s Dis. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13904","DOI":"10.1073\/pnas.1308335110","article-title":"Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system","volume":"110","author":"Jao","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"610","DOI":"10.2144\/000112619","article-title":"Method for isolation of PCR-ready genomic DNA from zebrafish tissues","volume":"43","author":"Meeker","year":"2007","journal-title":"Biotechniques"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1016\/j.yexcr.2009.06.023","article-title":"Independent and cooperative action of Psen2 with Psen1 in zebrafish embryos","volume":"315","author":"Nornes","year":"2009","journal-title":"Exp. Cell Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6069","DOI":"10.1038\/s41467-020-19892-6","article-title":"An expanded palette of improved SPLICS reporters detects multiple organelle contacts in vitro and in vivo","volume":"11","author":"Vallese","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0076-6879(09)05013-7","article-title":"Functional characterization of phosphorylation sites in dynamin-related protein 1","volume":"457","author":"Cribbs","year":"2009","journal-title":"Methods Enzymol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00438-013-0750-z","article-title":"Generation and application of signaling pathway reporter lines in zebrafish","volume":"288","author":"Moro","year":"2013","journal-title":"Mol. Genet. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.pneurobio.2014.03.001","article-title":"Zebrafish models of human motor neuron diseases: Advantages and limitations","volume":"118","author":"Babin","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.scitotenv.2018.08.421","article-title":"Development of a vibrational startle response assay for screening environmental pollutants and drugs impairing predator avoidance","volume":"650","author":"Faria","year":"2019","journal-title":"Sci. Total. Environ."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Theodoridi, A., Dinarello, A., Badenetti, L., Pavlidis, M., Valle, L.D., and Tsalafouta, A. (2021). Knockout of the hsd11b2 Gene Extends the Cortisol Stress Response in Both Zebrafish Larvae and Adults. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212525"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.schres.2017.05.034","article-title":"Acoustic startle response and its modulation in schizophrenia and autism spectrum disorder in Asian subjects","volume":"198","author":"Takahashi","year":"2018","journal-title":"Schizophr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/WNR.0000000000001056","article-title":"Suppressed acoustic startle response in traumatic brain injury masks post-traumatic stress disorder hyper-responsivity","volume":"29","author":"Liska","year":"2018","journal-title":"Neuroreport"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1089\/neu.2014.3451","article-title":"Long-Lasting Suppression of Acoustic Startle Response after Mild Traumatic Brain Injury","volume":"32","author":"Pang","year":"2015","journal-title":"J. Neurotrauma"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rossi, A., Galla, L., Gomiero, C., Zentilin, L., Giacca, M., Giorgio, V., Cal\u00ec, T., Pozzan, T., Greotti, E., and Pizzo, P. (2021). Calcium Signaling and Mitochondrial Function in Presenilin 2 Knock-Out Mice: Looking for Any Loss-of-Function Phenotype Related to Alzheimer\u2019s Disease. Cells, 10.","DOI":"10.3390\/cells10020204"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/s41418-017-0033-z","article-title":"SPLICS: A split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition","volume":"25","author":"Cieri","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5287","DOI":"10.1038\/s41596-021-00614-1","article-title":"Quantification of organelle contact sites by split-GFP-based contact site sensors (SPLICS) in living cells","volume":"16","author":"Brini","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-981-10-4567-7_4","article-title":"Endoplasmic Reticulum-Mitochondria Communication Through Ca2+ Signaling: The Importance of Mitochondria-Associated Membranes (MAMs)","volume":"997","author":"Marchi","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"653828","DOI":"10.3389\/fcell.2021.653828","article-title":"Endoplasmic Reticulum\u2013Mitochondria Contact Sites\u2014Emerging Intracellular Signaling Hubs","volume":"9","author":"Hirabayashi","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3389\/fcell.2020.00595","article-title":"Mitochondria-Associated ER Membranes\u2014The Origin Site of Autophagy","volume":"8","author":"Yang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ceca.2017.01.003","article-title":"The endoplasmic reticulum-mitochondria coupling in health and disease: Molecules, functions and significance","volume":"62","author":"Filadi","year":"2017","journal-title":"Cell Calcium"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2020.1797280","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)","volume":"17","author":"Klionsky","year":"2020","journal-title":"Autophagy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"232009","DOI":"10.1242\/jcs.232009","article-title":"Mitochondrial NCKX5 regulates melanosomal biogenesis and pigment production","volume":"132","author":"Zhang","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pizzo, P., Basso, E., Filadi, R., Greotti, E., Leparulo, A., Pendin, D., Redolfi, N., Rossini, M., Vajente, N., and Pozzan, T. (2020). Presenilin-2 and Calcium Handling: Molecules, Organelles, Cells and Brain Networks. Cells, 9.","DOI":"10.3390\/cells9102166"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrneurol.2009.218","article-title":"The secretases: Enzymes with therapeutic potential in Alzheimer disease","volume":"6","author":"Vassar","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102343","DOI":"10.1016\/j.ceca.2020.102343","article-title":"Mitochondria Associated Membranes (MAMs): Architecture and physiopathological role","volume":"94","author":"Barazzuol","year":"2021","journal-title":"Cell Calcium"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbadis.2013.10.015","article-title":"Oxidative stress and mitochondrial dysfunction in Alzheimer\u2019s disease","volume":"1842","author":"Wang","year":"2014","journal-title":"Biochim. Biophys. Mol. Basis Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.biopsych.2019.05.008","article-title":"Autophagy Dysfunction in Alzheimer\u2019s Disease: Mechanistic Insights and New Therapeutic Opportunities","volume":"87","author":"Curtis","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.4103\/1673-5374.262584","article-title":"Defective autophagy and Alzheimer\u2019s disease: Is calcium the key?","volume":"14","author":"Filadi","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.3892\/mmr.2016.5059","article-title":"Functionally conserved effects of rapamycin exposure on zebrafish","volume":"13","author":"Sucularli","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1684\/ejd.2020.3930","article-title":"The role of autophagy in skin pigmentation","volume":"30","author":"Zhu","year":"2020","journal-title":"Eur. J. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1242\/dev.099804","article-title":"Involvement of Delta\/Notch signaling in zebrafish adult pigment stripe patterning","volume":"141","author":"Hamada","year":"2014","journal-title":"Development"},{"key":"ref_58","first-page":"305","article-title":"Normal pigmentation: Histology, cellular biology, and biochemistry","volume":"16","author":"Quevedo","year":"1979","journal-title":"Ala. J. Med Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/0092-8674(84)90411-2","article-title":"Microtubule polarity and the direction of pigment transport reverse simultaneously in surgically severed melanophore arms","volume":"37","author":"McNiven","year":"1984","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1006\/dbio.2001.0418","article-title":"How the Zebrafish Gets Its Stripes","volume":"240","author":"Rawls","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cub.2014.01.007","article-title":"Mitochondria and Melanosomes Establish Physical Contacts Modulated by Mfn2 and Involved in Organelle Biogenesis","volume":"24","author":"Daniele","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1523\/JNEUROSCI.1802-12.2013","article-title":"Presenilin1 Regulates Histamine Neuron Development and Behavior in Zebrafish, Danio rerio","volume":"33","author":"Sundvik","year":"2013","journal-title":"J. Neurosci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/3\/376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:31Z","timestamp":1760119891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/3\/376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,19]]},"references-count":62,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["cells12030376"],"URL":"https:\/\/doi.org\/10.3390\/cells12030376","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,19]]}}}