Neuroscience 2005 Abstract
| Presentation Number: | 789.19 |
|---|---|
| Abstract Title: | Effect of caspase-6 activation on cytoskeletal integrity in human primary neurons. |
| Authors: |
Rousselet, E.*1,2
; Godefroy, N.1,2
; Petzke, T. L.1,2
; Goodyer, C. G.3
; LeBlanc, A. C.1,2
1 , Lady Davis Inst., Montreal, Canada 2PQ, 3999 Cote Sainte Catherine, H3T 1E2, 3Canada, 3999 Cote Sainte Catherine, H3T 1E2, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurodegenerative and Movement Disorders -- Alzheimer's disease: APP and presenilin -- other mechanisms |
| Session: |
789. Neurotoxicity: Apoptosis, Genes, and Viruses Poster |
| Presentation Time: | Tuesday, November 15, 2005 3:00 PM-4:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # TT66 |
| Keywords: | Alzheimer's disease, Apoptosis, Neurodegeneration, Caspase-6 substrates |
Caspase-6 (Csp-6) is activated in the early stages in Alzheimer’s disease and is sequestered to the neurites of neuropil threads, neuritic plaques and neurofibrillary tangles (Guo et al., A.J.P., 2004), suggesting a role for Csp-6 in neurodegeneration. Many Csp-6 substrates in non-neuronal cells types are intermediate filament proteins like vimentin, cytokeratin 18 and desmin or microtubule-associated protein, tau. Proteomic analysis allowed us to identify Csp-6 substrates (Petzke et al., SfN, 2005). Two of these, beta-actin and alpha-tubulin, are cytoskeleton proteins. The objective of this work is to determine the effect of Csp-6-cleaved beta-actin and alpha-tubulin on the cytoskeleton structure. In vitro, beta-actin is cleaved by Csp-6 at 3 different sites: after aspartate 14, aspartate 179 and aspartate 244. Beta-actin cleavage by Csp-6 at aspartate 244 is the same site previously described to be cleaved by Csp-3 and this cleavage site is recognized by the neoepitope Fractin antibody (kind gift from Greg Cole). This fragment is observed in serum-deprived human primary neurons where Csp-6 is activated. In human primary neurons deprived of serum, the cytoskeleton is altered at an early stage, prior to DNA fragmentation. The apparition of tubulin-stained varicosities, punctuate staining of MAP-2 and a disruption of neurofilament staining is observed in human primary neurons within 24 hours of serum deprivation, when the morphology of the neurites is preserved. This data shows that Csp-6 directly cleaves beta-actin and alpha-tubulin and thus may alter the cytoskeleton structure. These alterations may subsequently disrupt organelle trafficking and may be responsible for the neuronal dysfunction observed in the early stages of Alzheimer’s disease.
Supported by FRSQ and CIHR MOP 15118 to ALB
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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