{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:13:55Z","timestamp":1780085635584,"version":"3.54.0"},"reference-count":82,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,5]],"date-time":"2016-06-05T00:00:00Z","timestamp":1465084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005416","name":"The Norwegian Research Council","doi-asserted-by":"crossref","award":["204761\/F20"],"award-info":[{"award-number":["204761\/F20"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Western Norway Health Authority","award":["911630"],"award-info":[{"award-number":["911630"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>Although mutations in the leucine\u2010rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and\/or locomotion. This study shows that \u223c50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of \u03b2\u2010synuclein, PARK13, and SOD1 and causes \u03b2\u2010synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23754","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T04:42:46Z","timestamp":1465188166000},"page":"717-735","source":"Crossref","is-referenced-by-count":47,"title":["LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation"],"prefix":"10.1002","volume":"94","author":[{"given":"Shubhangi","family":"Prabhudesai","sequence":"first","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima Zahra","family":"Bensabeur","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashed","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indranil","family":"Basak","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solange","family":"Baez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Alves","sequence":"additional","affiliation":[{"name":"The Norwegian Centre for Movement Disorders Stavanger University Hospital Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia G.","family":"Holtzman","sequence":"additional","affiliation":[{"name":"Department of Biology Queens College and The Graduate Center, CUNY Queens New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Petter","family":"Larsen","sequence":"additional","affiliation":[{"name":"The Norwegian Centre for Movement Disorders Stavanger University Hospital Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Geir","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences St. John's University Queens New York"},{"name":"The Norwegian Centre for Movement Disorders Stavanger University Hospital Stavanger Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,6,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200539"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.201"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4552"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080705"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.01.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq275"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-102"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077209"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.07.028"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1242\/dev.123.1.129","article-title":"Mutations affecting development of the midline and general body shape during zebrafish embryogenesis","volume":"123","author":"Brand M","year":"1996","journal-title":"Development"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00219-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(01)01231-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2935"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.79"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20121742"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2015.11.009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad7297"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22172"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004090754"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.125.23.4655"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.560101.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21949"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi439"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-0189-3"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2007.07.007"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/450939"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/658270"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.62.5.436"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.04246.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-25"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/334345a0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702951200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103736200"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070209"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2009.257"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01882"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/33416"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0810123106"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2015.02.002"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.04.156"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1807-10.2010"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-010-9187-x"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12366"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.48"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.10.008"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.003194"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.03.006"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006070739"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100483"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.10.023"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9898"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004491"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1644"},{"key":"e_1_2_8_56_1","first-page":"67","volume-title":"Parkinson's disease and movement disorders","author":"Poewe W","year":"2007"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5321.2045"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0105-1"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.12.014"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020630"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00696-7"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0030078"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/159160"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.10884"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000914"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828250d6"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508052102"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21569"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.10.1546-b"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.63.9.1232"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-006-0075-8"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021519"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-7-2"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.04.469"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1096284"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8731-8"},{"key":"e_1_2_8_77_1","volume-title":"The zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio)","author":"Westerfield M","year":"2007"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2007.10.062"},{"key":"e_1_2_8_79_1","first-page":"F420","article-title":"Reversed polarity of Na+\u2010K+\u2010ATPase: mislocation to apical plasma membranes in polycystic kidney disease epithelia","volume":"260","author":"Wilson PD","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.11.034"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2010.04.002"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2016.01.157"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.11.005"}],"container-title":["Journal of Neuroscience Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjnr.23754","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jnr.23754","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T04:15:55Z","timestamp":1696479355000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jnr.23754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,5]]},"references-count":82,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/jnr.23754"],"URL":"https:\/\/doi.org\/10.1002\/jnr.23754","archive":["Portico"],"relation":{},"ISSN":["0360-4012","1097-4547"],"issn-type":[{"value":"0360-4012","type":"print"},{"value":"1097-4547","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,5]]}}}