{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:06:04Z","timestamp":1791187564008,"version":"4.1.0"},"reference-count":16,"publisher":"S. Karger AG","issue":"1-4","license":[{"start":{"date-parts":[[2011,12,23]],"date-time":"2011-12-23T00:00:00Z","timestamp":1324598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,12,23]],"date-time":"2011-12-23T00:00:00Z","timestamp":1324598400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2012]]},"abstract":"<jats:p>&lt;i&gt;Background:&lt;\/i&gt; Mutations in LRRK2 are associated with familial and sporadic Parkinson\u2019s disease (PD). Subjects with PD caused by LRRK2 mutations show pleiotropic pathology that can involve inclusions containing \u03b1-synuclein, tau or neither protein. The mechanisms by which mutations in LRRK2 lead to this pleiotropic pathology remain unknown. &lt;i&gt;Objectives:&lt;\/i&gt; To investigate mechanisms by which LRRK2 might cause PD. &lt;i&gt;Methods:&lt;\/i&gt; We used systems biology to investigate the transcriptomes from human brains, human blood cells and &lt;i&gt;Caenorhabditis elegans&lt;\/i&gt; expressing wild-type LRRK2. The role of autophagy was tested in lines of &lt;i&gt;C. elegans&lt;\/i&gt; expressing LRRK2, V337M tau or both proteins. Neuronal function was measured by quantifying thrashing. &lt;i&gt;Results:&lt;\/i&gt; Genes regulating autophagy were coordinately regulated with LRRK2. &lt;i&gt;C. elegans&lt;\/i&gt; expressing V337M tau showed reduced thrashing, as has been noted previously. Coexpressing mutant LRRK2 (R1441C or G2019S) with V337M tau increased the motor deficits. Treating the lines of &lt;i&gt;C. elegans&lt;\/i&gt; with an mTOR inhibitor that enhances autophagic flux, ridaforolimus, increased the thrashing behavior to the same level as nontransgenic nematodes. &lt;i&gt;Conclusion:&lt;\/i&gt; These data support a role for LRRK2 in autophagy, raise the possibility that deficits in autophagy contribute to the pathophysiology of LRRK2, and point to a potential therapeutic approach addressing the pathophysiology of LRRK2 in PD.<\/jats:p>","DOI":"10.1159\/000332599","type":"journal-article","created":{"date-parts":[[2011,12,23]],"date-time":"2011-12-23T08:02:55Z","timestamp":1324627375000},"page":"238-241","source":"Crossref","is-referenced-by-count":38,"title":["Regulation of Physiologic Actions of LRRK2: Focus on Autophagy"],"prefix":"10.1159","volume":"10","author":[{"given":"Andrew","family":"Ferree","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guillily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Takashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Squillace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Weigele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Wolozin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2011,12,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1042%2FAN20090007"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.0507360102"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1093%2Fhmg%2Fddl471"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.nbd.2006.04.001"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016%2Fj.bbrc.2007.04.006"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1371%2Fjournal.pgen.1000902"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M708718200"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1021%2Fbi100157u"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1074%2Fjbc.M111.234005"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038%2Fnature09191"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1111%2Fj.1471-4159.2008.05217.x"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1523%2FJNEUROSCI.2281-09.2009"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1371%2Fjournal.pbio.0050008"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1038%2Fnbt1075"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1073%2Fpnas.1533448100"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1158%2F1535-7163.MCT-10-0792"}],"container-title":["Neurodegenerative Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/332599","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/332599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:50:24Z","timestamp":1745434224000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000332599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,23]]},"references-count":16,"journal-issue":{"issue":"1-4","published-online":{"date-parts":[[2012,4,1]]},"published-print":{"date-parts":[[2012,4,19]]}},"URL":"https:\/\/doi.org\/10.1159\/000332599","archive":["Portico"],"relation":{},"ISSN":["1660-2854","1660-2862"],"issn-type":[{"value":"1660-2854","type":"print"},{"value":"1660-2862","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12,23]]}}}