| pubmed-article:18258746 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18258746 | lifeskim:mentions | umls-concept:C0026336 | lld:lifeskim |
| pubmed-article:18258746 | lifeskim:mentions | umls-concept:C0242422 | lld:lifeskim |
| pubmed-article:18258746 | lifeskim:mentions | umls-concept:C0013138 | lld:lifeskim |
| pubmed-article:18258746 | pubmed:issue | 7 | lld:pubmed |
| pubmed-article:18258746 | pubmed:dateCreated | 2008-2-21 | lld:pubmed |
| pubmed-article:18258746 | pubmed:abstractText | Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. To our knowledge, this is the first in vivo"gain-of-function" model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention. | lld:pubmed |
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| pubmed-article:18258746 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:18258746 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:18258746 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18258746 | pubmed:month | Feb | lld:pubmed |
| pubmed-article:18258746 | pubmed:issn | 1091-6490 | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:NBB | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:MontellCraigC | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:WangTaoT | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:RossChristoph... | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:SawaAkiraA | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:LiuZhaohuiZ | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:JiangHaibingH | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:WangXiaoyueX | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:MoranTimothyT | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:JiaoYuchenY | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:SmithWanli... | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:LiXuepingX | lld:pubmed |
| pubmed-article:18258746 | pubmed:author | pubmed-author:RenQiutingQ | lld:pubmed |
| pubmed-article:18258746 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:18258746 | pubmed:day | 19 | lld:pubmed |
| pubmed-article:18258746 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:18258746 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18258746 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18258746 | pubmed:pagination | 2693-8 | lld:pubmed |
| pubmed-article:18258746 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:18258746 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:18258746 | pubmed:articleTitle | A Drosophila model for LRRK2-linked parkinsonism. | lld:pubmed |
| pubmed-article:18258746 | pubmed:affiliation | Department of Psychiatry, Division of Neurobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. | lld:pubmed |
| pubmed-article:18258746 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18258746 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:18258746 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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