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Brief Communications

Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila

Chee-Hoe Ng, Shaun Z. S. Mok, Cherlyn Koh, Xuezhi Ouyang, Marc L. Fivaz, Eng-King Tan, Valina L. Dawson, Ted M. Dawson, Fengwei Yu and Kah-Leong Lim
Journal of Neuroscience 9 September 2009, 29 (36) 11257-11262; DOI: https://doi.org/10.1523/JNEUROSCI.2375-09.2009
Chee-Hoe Ng
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Shaun Z. S. Mok
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Cherlyn Koh
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Xuezhi Ouyang
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Marc L. Fivaz
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Eng-King Tan
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Valina L. Dawson
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Ted M. Dawson
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Fengwei Yu
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Kah-Leong Lim
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    Figure 1.

    Expression of LRRK2 transgenes in Drosophila neither affects its overall brain architecture nor triggers obvious eye abnormalities. A, Left, Anti-elav (green) and anti-LRRK2 (red) immunostaining of whole-mount adult brains derived from 2-d-old control or transgenic flies expressing wild-type human LRRK2, as indicated. Right, Enlarged images (and inset) show the localization of elav and LRRK2 signals to the nucleus and cytoplasm, respectively, in the brain of a wild-type LRRK2-expressing fly. An anti-myc immunoblot of brain lysates prepared from 2-d-old control or transgenic flies expressing various LRRK2 species is shown below (genotype: elav-Gal4/+ or elav–Gal4–hLRRK2). B, SEM eye images of 20-d-old GMR-Gal4/+ or GMR–Gal4–hLRRK adult flies. No retinal degeneration was observed in all flies examined.

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    Figure 2.

    Expression of LRRK2 mutants in flies promotes DA neurodegeneration and concomitant locomotion deficits. A, B, Bar graph showing the number of TH-positive DA neurons in different clusters of various fly species at 20 or 60 d after eclosion, as indicated (n = 10). C, Representative confocal microscopy images showing TH-positive (red) DA neurons in the PPM1 cluster (boxed) of 60-d-old control or LRRK2-expressing flies. Inset, Higher magnification of boxed regions. D, E, Bar graph showing the percentage of various male (D) and female (E) flies at different days after eclosion that reached the top of assay column after 1 min (n = 20) (genotype: ddc–Gal4/+ or ddc–Gal4–hLRRK2).

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    Figure 3.

    Exposure to rotenone accelerates DA degeneration in LRRK2 G2019 and G2385R mutant flies. A, Bar graph showing the number of TH-positive DA neurons in different clusters of various fly species at 15 d after rotenone treatment (n = 15). B, Representative confocal microscopy images showing TH-positive (red) DA neurons in the PPM3 cluster of various, rotenone-treated fly species, as indicated (genotype: ddc–Gal4/+ or ddc–Gal4–hLRRK2).

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    Figure 4.

    Parkin coexpression mitigates DA degeneration in LRRK2 G2019S-expressing flies in the presence or absence of rotenone. A, Bar graph showing the number of TH-positive DA neurons in different clusters of various fly species at 15 d after rotenone treatment (n = 15). B, Representative confocal microscopy images showing TH-positive (red) DA neurons in whole-mount adult brains derived from rotenone-treated flies expressing either LRRK2 G2019S alone or in the presence of parkin coexpression. Right, PPM3 cluster (circled) are shown at higher magnification. C, Bar graph showing the number of TH-positive DA neurons in different clusters of the various fly species at 60 d after eclosion, as indicated (n = 8) (genotype: ddc–Gal4/+ or ddc–Gal4–hLRRK2 or ddci-Gal4–hLRRK2;ddc–Gal4–hparkin).

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The Journal of Neuroscience: 29 (36)
Journal of Neuroscience
Vol. 29, Issue 36
9 Sep 2009
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Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila
Chee-Hoe Ng, Shaun Z. S. Mok, Cherlyn Koh, Xuezhi Ouyang, Marc L. Fivaz, Eng-King Tan, Valina L. Dawson, Ted M. Dawson, Fengwei Yu, Kah-Leong Lim
Journal of Neuroscience 9 September 2009, 29 (36) 11257-11262; DOI: 10.1523/JNEUROSCI.2375-09.2009

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Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila
Chee-Hoe Ng, Shaun Z. S. Mok, Cherlyn Koh, Xuezhi Ouyang, Marc L. Fivaz, Eng-King Tan, Valina L. Dawson, Ted M. Dawson, Fengwei Yu, Kah-Leong Lim
Journal of Neuroscience 9 September 2009, 29 (36) 11257-11262; DOI: 10.1523/JNEUROSCI.2375-09.2009
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