WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
 QUICK SEARCH:   [advanced]


     
-


HOME
  |  
SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 8, 2007, 27(32):8563-8570; doi:10.1523/JNEUROSCI.0218-07.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, C.
Right arrow Articles by Lim, K.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, C.
Right arrow Articles by Lim, K.-L.

 Previous Article  |  Next Article 

Neurobiology of Disease
Drosophila Overexpressing Parkin R275W Mutant Exhibits Dopaminergic Neuron Degeneration and Mitochondrial Abnormalities

Cheng Wang,1,3,4 Ruifeng Lu,3,4 Xuezhi Ouyang,3 Michelle W. L. Ho,1 William Chia,3,4 Fengwei Yu,3,4 and Kah-Leong Lim1,2,4

1Neurodegeneration Research Laboratory and 2Parkinson's Disease and Movement Disorders Center, National Neuroscience Institute, Singapore 308433, and 3Temasek Life Sciences Laboratory and 4Department of Biological Sciences, National University of Singapore, Singapore 117604

Correspondence should be addressed to either of the following: Dr. Kah-Leong Lim, Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Email: kah_leong_lim{at}nni.com.sg; or Dr. Fengwei Yu, Molecular Neurogenesis Group, Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Email: fengwei{at}tll.org.sg

Mutations in the parkin gene are a predominant cause of familial parkinsonism. Although initially described as a recessive disorder, emerging evidence suggest that single parkin mutations alone may confer increased susceptibility to Parkinson's disease. To better understand the effects of parkin mutations in vivo, we generated transgenic Drosophila overexpressing two human parkin missense mutants, R275W and G328E. Transgenic flies that overexpress R275W, but not wild-type or G328E, human parkin display an age-dependent degeneration of specific dopaminergic neuronal clusters and concomitant locomotor deficits that accelerate with age or in response to rotenone treatment. Furthermore, R275W mutant flies also exhibit prominent mitochondrial abnormalities in their flight muscles. Interestingly, these defects caused by the expression of human R275W parkin are highly similar to those triggered by the loss of endogenous parkin in parkin null flies. Together, our results provide the first in vivo evidence demonstrating that parkin R275W mutant expression mediates pathogenic outcomes and suggest the interesting possibility that select parkin mutations may directly exert neurotoxicity in vivo.

Key words: Parkinson's disease; ubiquitin; proteasome; rotenone; neurotoxicity; neuronal death


Received Sept. 15, 2006; revised June 26, 2007; accepted June 29, 2007.

Correspondence should be addressed to either of the following: Dr. Kah-Leong Lim, Neurodegeneration Research Laboratory, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Email: kah_leong_lim{at}nni.com.sg; or Dr. Fengwei Yu, Molecular Neurogenesis Group, Temasek Life Sciences Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Email: fengwei{at}tll.org.sg




This article has been cited by other articles:


Home page
Hum Mol GenetHome page
A. K. Berger, G. P. Cortese, K. D. Amodeo, A. Weihofen, A. Letai, and M. J. LaVoie
Parkin selectively alters the intrinsic threshold for mitochondrial cytochrome c release
Hum. Mol. Genet., November 15, 2009; 18(22): 4317 - 4328.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
C.-H. Ng, S. Z. S. Mok, C. Koh, X. Ouyang, M. L. Fivaz, E.-K. Tan, V. L. Dawson, T. M. Dawson, F. Yu, and K.-L. Lim
Parkin Protects against LRRK2 G2019S Mutant-Induced Dopaminergic Neurodegeneration in Drosophila
J. Neurosci., September 9, 2009; 29(36): 11257 - 11262.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
M. P. Hart and A. Xu
Mice Expressing Mutant Parkin Exhibit Hallmark Features of Parkinson's Disease
J. Neurosci., June 10, 2009; 29(23): 7392 - 7394.
[Full Text] [PDF]


Home page
J. Med. Genet.Home page
J Brooks, J Ding, J Simon-Sanchez, C Paisan-Ruiz, A B Singleton, and S W Scholz
Parkin and PINK1 mutations in early-onset Parkinson's disease: comprehensive screening in publicly available cases and control
J. Med. Genet., June 1, 2009; 46(6): 375 - 381.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
X.-H. Lu, S. M. Fleming, B. Meurers, L. C. Ackerson, F. Mortazavi, V. Lo, D. Hernandez, D. Sulzer, G. R. Jackson, N. T. Maidment, et al.
Bacterial Artificial Chromosome Transgenic Mice Expressing a Truncated Mutant Parkin Exhibit Age-Dependent Hypokinetic Motor Deficits, Dopaminergic Neuron Degeneration, and Accumulation of Proteinase K-Resistant {alpha}-Synuclein
J. Neurosci., February 18, 2009; 29(7): 1962 - 1976.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
R. Wassef, R. Haenold, A. Hansel, N. Brot, S. H. Heinemann, and T. Hoshi
Methionine Sulfoxide Reductase A and a Dietary Supplement S-Methyl-L-Cysteine Prevent Parkinson's-Like Symptoms
J. Neurosci., November 21, 2007; 27(47): 12808 - 12816.
[Abstract] [Full Text] [PDF]



-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help

-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-