Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila
- Danling Wang*,†,
- Li Qian*,
- Hui Xiong*,
- Jiandong Liu*,
- Wendi S. Neckameyer‡,
- Sean Oldham*,
- Kun Xia§,
- Jianzhi Wang†,
- Rolf Bodmer*,¶, and
- Zhuohua Zhang*,§,¶
- *Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037;
- †Department of Pathophysiology, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China;
- ‡Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, MO 63104; and
- §National Laboratory of Medical Genetics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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Edited by Lily Y. Jan, University of California School of Medicine, San Francisco, CA, and approved July 12, 2006 (received for review June 5, 2006)
Abstract
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.
Footnotes
- ¶To whom correspondence may be addressed. E-mail: benzz{at}burnham.org or rolf{at}burnham.org
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Author contributions: R.B. and Z.Z. designed research; D.W., L.Q., H.X., J.L., and K.X. performed research; W.S.N. contributed new reagents/analytic tools; S.O., J.W., R.B., and Z.Z. analyzed data; and R.B. and Z.Z. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
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See Commentary on page 13269.
- Abbreviations:
- DA,
- dopaminergic;
- PD,
- Parkinson's disease;
- VUM,
- unpaired ventral medial cluster;
- TH,
- tyrosine hydroxylase
- © 2006 by The National Academy of Sciences of the USA
