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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2015,9,29]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Propagation of protein aggregates throughout the nervous system is thought to play a significant role in the pathology of neurodegenerative diseases. Thus, understanding how this propagation is regulated is crucial for identifying potential therapeutic interventions. Here we use experimental advantages of\n                    <jats:italic>Drosophila<\/jats:italic>\n                    to investigate aggregate spreading. We demonstrate that huntingtin, containing an expanded polyglutamine tract of 138 repeats, but not an unexpanded form, aggregates and spreads rapidly throughout the brain, resulting in loss of vulnerable neurons. Aggregate spreading and neuronal loss are impaired by blocking synaptic exocytosis in releasing cells or endocytic uptake in target cells. These studies enable screens for genetic and pharmacological modifiers that could ameliorate the deleterious effects of spreading in neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1516217112","type":"journal-article","created":{"date-parts":[[2015,9,8]],"date-time":"2015-09-08T22:21:21Z","timestamp":1441750881000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["Transcellular spreading of huntingtin aggregates in the\n                    <i>Drosophila<\/i>\n                    brain"],"prefix":"10.1073","volume":"112","author":[{"given":"Daniel T.","family":"Babcock","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, University of Wisconsin, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Ganetzky","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics, University of Wisconsin, Madison, WI 53706"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2015,9,8]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-002-0808-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000261045.57095.56"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000260965.20021.47"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2004.02.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.12.040"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3457"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3761"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35006074"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040584"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81200-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00594-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80573-5"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0400243101"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35099568"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7768"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1681"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.133710"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.04.026"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1089035"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075420"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/01677060802471627"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.24397"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.09.011"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1204520109"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.01.001"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81385-9"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221450198"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(01)02125-5"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10250.1998"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.114.172403"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05954"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00168-3"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(06)75002-5"},{"key":"e_1_3_3_39_2","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/j.1471-4159.2010.06672.x","article-title":"Differential vulnerability of neurons in Huntington\u2019s disease: The role of cell type-specific features","volume":"113","author":"Han I","year":"2010","unstructured":"I Han, Y You, JH Kordower, ST Brady, GA Morfini, Differential vulnerability of neurons in Huntington\u2019s disease: The role of cell type-specific features. 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