QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 2, 2003, 23(13):5455-5460

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Kang, S. J. Articles by Yuan, J. Search for Related Content PubMed PubMed Citation Articles by Kang, S. J. Articles by Yuan, J.

 Previous Article  |  Next Article 

Dissociation between Neurodegeneration and Caspase-11-Mediated Activation of Caspase-1 and Caspase-3 in a Mouse Model of Amyotrophic Lateral Sclerosis

Shin Jung Kang, Ivelisse Sanchez, Naisen Jing, and Junying Yuan

Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115

Caspase-11 is a key regulator of caspase-1 and caspase-3 activation under pathological conditions. We show here that the expression of caspase-11 is upregulated in the spinal cord of superoxide dismutase 1 (SOD1) G93A transgenic mice, a mouse model of amyotrophic lateral sclerosis (ALS), before the onset of motor dysfunction and remains at the high levels throughout the course of disease. The caspase-1- and caspase-3-like activities, as well as the level of interleukin-1, were significantly reduced in the spinal cord of symptomatic caspase-11–/–;SOD1 G93A mice compared with that of caspase-11+/–; SOD1 G93A mice. However, neurodegeneration, inflammatory responses, and the disease onset and progression in SOD1 G93A transgenic mice were not altered by the ablation of caspase-11 gene. Thus, although caspases may contribute to certain aspects of pathology in this mouse model of ALS, their inhibition is not sufficient to prevent neurodegeneration. Our study urges caution when considering the inhibition of caspases as a direct therapeutic method for the treatment of chronic neurodegenerative diseases.

Key words: ALS; motor neuron degeneration; neurodegeneration; SOD1; caspase; apoptosis

---

Received Feb. 14, 2003; revised Apr. 24, 2003; accepted Apr. 24, 2003.

This article has been cited by other articles:

				D. Kieran, I. Woods, A. Villunger, A. Strasser, and J. H. M. Prehn Deletion of the BH3-only protein puma protects motoneurons from ER stress-induced apoptosis and delays motoneuron loss in ALS mice PNAS, December 18, 2007; 104(51): 20606 - 20611. [Abstract] [Full Text] [PDF]

				A. D. Steele, O. D. King, W. S. Jackson, C. A. Hetz, A. W. Borkowski, P. Thielen, R. Wollmann, and S. Lindquist Diminishing Apoptosis by Deletion of Bax or Overexpression of Bcl-2 Does Not Protect against Infectious Prion Toxicity In Vivo J. Neurosci., November 21, 2007; 27(47): 13022 - 13027. [Abstract] [Full Text] [PDF]

				A. D. Steele and C. H. Yi Neuromuscular Denervation: Bax up against the Wall in Amyotrophic Lateral Sclerosis J. Neurosci., December 13, 2006; 26(50): 12849 - 12851. [Full Text] [PDF]

				T. W. Gould, R. R. Buss, S. Vinsant, D. Prevette, W. Sun, C. M. Knudson, C. E. Milligan, and R. W. Oppenheim Complete Dissociation of Motor Neuron Death from Motor Dysfunction by Bax Deletion in a Mouse Model of ALS. J. Neurosci., August 23, 2006; 26(34): 8774 - 8786. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help