{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:40:31Z","timestamp":1761561631476},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,5,9]],"date-time":"2012-05-09T00:00:00Z","timestamp":1336521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:sec><jats:label \/><jats:p><jats:italic>J. Neurochem.<\/jats:italic> (2012) <jats:bold>122<\/jats:bold>, 196\u2013207.<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Many genes associated with familial Parkinson\u2019s disease contribute to mitochondrial morphology and function. Some of these genes, for example, <jats:italic>Pink1<\/jats:italic> and <jats:italic>Parkin<\/jats:italic>, are part of a common pathway. The presenilin\u2010associated rhomboid\u2010like (<jats:italic>PARL<\/jats:italic>) gene was recently linked to familial Parkinson\u2019s disease. The <jats:italic>PARL<\/jats:italic> gene product is found in the inner mitochondrial membrane and cleaves the optic atrophy 1 protein, involved in mitochondrial morphology and apoptosis. In <jats:italic>Drosophila<\/jats:italic>, the <jats:italic>PARL<\/jats:italic>\u2010related <jats:italic>rhomboid\u20107<\/jats:italic> gene acts upstream of <jats:italic>pink1<\/jats:italic> and <jats:italic>parkin<\/jats:italic>. However, such a genetic relationship is still unknown in vertebrates. Here, we show that the zebrafish genome comprises two <jats:italic>parl<\/jats:italic> paralogs: <jats:italic>parla<\/jats:italic> and <jats:italic>parlb<\/jats:italic>. Morpholino\u2010mediated loss of <jats:italic>parla<\/jats:italic> and\/or <jats:italic>parlb<\/jats:italic> function resulted in mild neurodegeneration, as evidenced by a lower density of dopaminergic neurons. Patterning of dopaminergic neurons was also perturbed in the ventral diencephalon. Morphants exhibited extensive cell death throughout the entire body as well as increased larval mortality. The morphant phenotype could be rescued by injection of human <jats:italic>PARL<\/jats:italic> mRNA, but not catalytically inactive <jats:italic>PARL<\/jats:italic>, suggesting functional conservation between the human and zebrafish proteins. More importantly, the zebrafish <jats:italic>pink1<\/jats:italic> mRNA as well as the human <jats:italic>PINK1<\/jats:italic> mRNA, but not kinase\u2010dead nor Parkinson\u2019s disease\u2010linked mutant <jats:italic>PINK1<\/jats:italic> mRNA, also rescued the morphant phenotype, providing evidence that <jats:italic>Parl<\/jats:italic> genes may function upstream of <jats:italic>Pink1<\/jats:italic>, as part of a conserved pathway in vertebrates.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2012.07758.x","type":"journal-article","created":{"date-parts":[[2012,4,16]],"date-time":"2012-04-16T16:54:46Z","timestamp":1334595286000},"page":"196-207","source":"Crossref","is-referenced-by-count":15,"title":["Zebrafish Parla\u2010 and Parlb\u2010deficiency affects dopaminergic neuron patterning and embryonic survival"],"prefix":"10.1111","volume":"122","author":[{"given":"Sandra","family":"Noble","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abid","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Godoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanwei","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Ekker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,5,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0979-08.2008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-4-12"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04291.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.021"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.74.082803.133400"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq526"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1831"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011783"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp108"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.025"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.14"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705363105"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211311200"},{"key":"e_1_2_7_16_1","first-page":"1","article-title":"Dopamine transporter expression distinguishes dopaminergic neurons form other catecholaminergic neurons in the developing zebrafish embryo","volume":"10","author":"Holzschuh J.","year":"2001","journal-title":"Mech. 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