| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-49 |
DRI_Approach |
denotes |
A Drosophila model for LRRK2-linked parkinsonism. |
| T2 |
50-196 |
DRI_Challenge |
denotes |
Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. |
| T3 |
197-306 |
DRI_Outcome |
denotes |
Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. |
| T4 |
307-475 |
DRI_Outcome |
denotes |
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. |
| T5 |
476-590 |
DRI_Background |
denotes |
Expression of either wild-type human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. |
| T6 |
591-742 |
DRI_Background |
denotes |
Expression of LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. |
| T7 |
743-882 |
DRI_Challenge |
denotes |
Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of wild-type LRRK2. |
| T8 |
883-1026 |
DRI_Challenge |
denotes |
Treatment with l-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase-positive neurons. |
| T9 |
1027-1171 |
DRI_Outcome |
denotes |
To our knowledge, this is the first in vivo"gain-of-function" model which recapitulates several key features of LRRK2-linked human parkinsonism. |
| T10 |
1172-1305 |
DRI_Challenge |
denotes |
These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention. |
