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


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, April 13, 2005, 25(15):3801-3812; doi:10.1523/JNEUROSCI.5157-04.2005

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 (38)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cao, S.
Right arrow Articles by Caldwell, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cao, S.
Right arrow Articles by Caldwell, G. A.

 Previous Article  |  Next Article 

Neurobiology of Disease
Torsin-Mediated Protection from Cellular Stress in the Dopaminergic Neurons of Caenorhabditis elegans

Songsong Cao, Christopher C. Gelwix, Kim A. Caldwell, and Guy A. Caldwell

Department of Biological Sciences, The University of Alabama, Tuscaloosa, Alabama 35487

Parkinson's disease (PD) is linked genetically to proteins that function in the management of cellular stress resulting from protein misfolding and oxidative damage. Overexpression or mutation of {alpha}-synuclein results in the formation of Lewy bodies and neurodegeneration of dopaminergic (DA) neurons. Human torsinA, mutations in which cause another movement disorder termed early-onset torsion dystonia, is highly expressed in DA neurons and is also a component of Lewy bodies. Previous work has established torsins as having molecular chaperone activity. Thus, we examined the ability of torsinA to manage cellular stress within DA neurons of the nematode Caenorhabditis elegans. Worm DA neurons undergo a reproducible pattern of neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), a neurotoxin commonly used to model PD. Overexpression of torsins in C. elegans DA neurons results in dramatic suppression of neurodegeneration after 6-OHDA treatment. In contrast, expression of either dystonia-associated mutant torsinA or combined overexpression of wild-type and mutant torsinA yielded greatly diminished neuroprotection against 6-OHDA. We further demonstrated that torsins seem to protect DA neurons from 6-OHDA through downregulating protein levels of the dopamine transporter (DAT-1) in vivo. Additionally, we determined that torsins protect robustly against DA neurodegeneration caused by overexpression of {alpha}-synuclein. Using mutant nematodes lacking DAT-1 function, we also showed that torsin neuroprotection from {alpha}-synuclein-induced degeneration occurs in a manner independent of this transporter. Together, these data have mechanistic implications for movement disorders, because our results demonstrate that torsin proteins have the capacity to manage sources of cellular stress within DA neurons.

Key words: dopamine; dystonia; Parkinson; torsin; C. elegans; synuclein

Received Aug 30, 2004; revised February 20, 2005; accepted February 21, 2005.




This article has been cited by other articles:


Home page
 NeurologyHome page
M. Carbon, M. Niethammer, S. Peng, D. Raymond, V. Dhawan, T. Chaly, Y. Ma, S. Bressman, and D. Eidelberg
Abnormal striatal and thalamic dopamine neurotransmission: Genotype-related features of dystonia
Neurology, June 16, 2009; 72(24): 2097 - 2103.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. C. K. Leung, P. L. Williams, A. Benedetto, C. Au, K. J. Helmcke, M. Aschner, and J. N. Meyer
Caenorhabditis elegans: An Emerging Model in Biomedical and Environmental Toxicology
Toxicol. Sci., November 1, 2008; 106(1): 5 - 28.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Kuwahara, A. Koyama, S. Koyama, S. Yoshina, C.-H. Ren, T. Kato, S. Mitani, and T. Iwatsubo
A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in {alpha}-synuclein transgenic C. elegans
Hum. Mol. Genet., October 1, 2008; 17(19): 2997 - 3009.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
L. Zhu, J. O. Wrabl, A. P. Hayashi, L. S. Rose, and P. J. Thomas
The Torsin-family AAA+ Protein OOC-5 Contains a Critical Disulfide Adjacent to Sensor-II That Couples Redox State to Nucleotide Binding
Mol. Biol. Cell, August 1, 2008; 19(8): 3599 - 3612.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. W. Hewett, F. C. Nery, B. Niland, P. Ge, P. Tan, P. Hadwiger, B. A. Tannous, D. W.Y. Sah, and X. O. Breakefield
siRNA knock-down of mutant torsinA restores processing through secretory pathway in DYT1 dystonia cells
Hum. Mol. Genet., May 15, 2008; 17(10): 1436 - 1445.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Hamamichi, R. N. Rivas, A. L. Knight, S. Cao, K. A. Caldwell, and G. A. Caldwell
Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model
PNAS, January 15, 2008; 105(2): 728 - 733.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. W. Hewett, B. Tannous, B. P. Niland, F. C. Nery, J. Zeng, Y. Li, and X. O. Breakefield
Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells
PNAS, April 24, 2007; 104(17): 7271 - 7276.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Chaudhuri, K. Bowling, C. Funderburk, H. Lawal, A. Inamdar, Z. Wang, and J. M. O'Donnell
Interaction of Genetic and Environmental Factors in a Drosophila Parkinsonism Model
J. Neurosci., March 7, 2007; 27(10): 2457 - 2467.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
C. T. Esapa, A. Waite, M. Locke, M. A. Benson, M. Kraus, R.A. J. McIlhinney, R. V. Sillitoe, P. W. Beesley, and D. J. Blake
SGCE missense mutations that cause myoclonus-dystonia syndrome impair {varepsilon}-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA
Hum. Mol. Genet., February 1, 2007; 16(3): 327 - 342.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. A. Cooper, A. D. Gitler, A. Cashikar, C. M. Haynes, K. J. Hill, B. Bhullar, K. Liu, K. Xu, K. E. Strathearn, F. Liu, et al.
{alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models
Science, July 21, 2006; 313(5785): 324 - 328.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
W. Springer, T. Hoppe, E. Schmidt, and R. Baumeister
A Caenorhabditis elegans Parkin mutant with altered solubility couples {alpha}-synuclein aggregation to proteotoxic stress
Hum. Mol. Genet., November 15, 2005; 14(22): 3407 - 3423.
[Abstract] [Full Text] [PDF]


-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-