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


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, March 8, 2006, 26(10):2738-2744; doi:10.1523/JNEUROSCI.4834-05.2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 ISI 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 ISI Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hallows, J. L.
Right arrow Articles by Vincent, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hallows, J. L.
Right arrow Articles by Vincent, I.

 Previous Article  |  Next Article 

Neurobiology of Disease
p35/p25 Is Not Essential for Tau and Cytoskeletal Pathology or Neuronal Loss in Niemann–Pick Type C Disease

Janice L. Hallows, Robert E. Iosif, Rebecca D. Biasell, and Inez Vincent

Department of Pathology, University of Washington, Seattle, Washington 98195

Correspondence should be addressed to Inez Vincent at her present address: Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5A 4H4. Email: ivincent{at}cmmt.ubc.ca

Hyperactivation of the cyclin-dependent kinase 5 (cdk5), triggered by proteolytic conversion of its neuronal activator, p35, to a more potent byproduct, p25, has been implicated in Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Niemann–Pick type C disease (NPC). This mechanism is thought to lead to the development of neuropathological hallmarks, i.e., hyperphosphorylated cytoskeletal proteins, neuronal inclusions, and neurodegeneration, that are common to all three diseases. This pathological ensemble is recapitulated in a single model, the npc-1 (npc–/–) mutant mouse. Previously, we showed that pharmacological cdk inhibitors dramatically reduced hyperphosphorylation, lesion formation, and locomotor defects in npc–/– mice, suggesting that cdk activity is required for NPC pathogenesis. Here, we used genetic ablation of the p35 gene to examine the specific involvement of p35, p25, and hence cdk5 activation in NPC neuropathogenesis. We found that lack of p35/p25 does not slow the onset or progression or improve the neuropathology of NPC. Our results provide direct evidence that p35/p25-mediated cdk5 deregulation is not essential for NPC pathology and suggest that similar pathology in AD may also be cdk5 independent.

Key words: Alzheimer's disease; ALS; cdk5; hyperphosphorylation; spheroid; tauopathy

Received Nov. 9, 2005; revised Jan. 30, 2006; accepted Feb. 1, 2006.

Correspondence should be addressed to Inez Vincent at her present address: Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5A 4H4. Email: ivincent{at}cmmt.ubc.ca






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-