Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila.
Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder. Mutations in the PINK1 gene are linked to the autosomal recessive early onset familial form of PD. The physiological function of PINK1 and pathological abnormality of PD-associated PINK1 mutants are largely unknown. We here show that inactivation of Drosophila PINK1 (dPINK1) using RNAi results in progressive loss of dopaminergic neurons and in ommatidial degeneration of the compound eye, which is rescued by expression of human PINK1 (hPINK1). Expression of human SOD1 suppresses neurodegeneration induced by dPINK1 inactivation. Moreover, treatment of dPINK1 RNAi flies with the antioxidants SOD and vitamin E significantly inhibits ommatidial degeneration. Thus, dPINK1 plays an essential role in maintaining neuronal survival by preventing neurons from undergoing oxidative stress, thereby suggesting a potential mechanism by which a reduction in PINK1 function leads to PD-associated neurodegeneration.
Wang
Danling
D
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Qian
Li
L
Xiong
Hui
H
Liu
Jiandong
J
Neckameyer
Wendi S
WS
Oldham
Sean
S
Xia
Kun
K
Wang
Jianzhi
J
Bodmer
Rolf
R
Zhang
Zhuohua
Z
D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D020868:Gene Silencing; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000209:etiology; D020011:Protective Agents / Q000378:metabolism / Q000494:pharmacology*; D011494:Protein Kinases; D034622:RNA Interference; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000378:metabolism / Q000494:pharmacology; D000099202:PTEN-Induced Putative Kinase
D000975:Antioxidants; D018076:DNA, Complementary; D029721:Drosophila Proteins; D020011:Protective Agents; D011494:Protein Kinases; D013482:Superoxide Dismutase; D014810:Vitamin E; D000099202:PTEN-Induced Putative Kinase