Neuroscience 2005 Abstract
| Presentation Number: | 80.9 |
|---|---|
| Abstract Title: | Substrates of caspase-6 in human primary neurons: a proteomic study. |
| Authors: |
Petzke, T. L.*1
; Rousselet, E.1,2
; Goodyer, C. G.3
; LeBlanc, A. C.1,2
1Lady Davis Inst., Montreal, Canada 2PQ, 3999 Cote Ste-Catherine, H3T 1E2, 3Canada, 3999 Cote Ste-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: |
80. Molecular Profiling of Neurodegenerative Disease Poster |
| Presentation Time: | Saturday, November 12, 2005 1:00 PM-2:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # KK22 |
| Keywords: | Alzheimer's Disease, Apoptosis, Neurodegeneration, Cytoskeleton |
The activation of caspase-6 (Csp-6) is observed in Alzheimer’s Disease (AD) and mild cognitive impairment (MCI) (Guo et al., 2004, Am. J. Pathol., LeBlanc et al., SfN 2005). This activation is involved at an early stage of AD since immunoreactivity of active Csp-6 and Csp-6-cleaved tau is observed in MCI and in pretangles of AD brains. Active Csp-6 is found localized in the neurites or tangles but not in the nucleus of AD neurons, in contrast to its nuclear localization in ischemic brain apoptotic neurons. In other cell types, Csp-6 has been shown to cleave several intermediate filament proteins. These results suggest that active Csp-6 may lead to neuronal dysfunction before eventual cell death in MCI and AD by affecting the cytoskeleton of the neuron. This led us to study the substrates of Csp-6 in human primary neurons. Human primary neurons were fractionated to give protein fractions enriched in nuclear, membrane and cytosolic proteins. These proteins were in turn digested with recombinant active Csp-6 (R-csp-6). Samples digested with R-csp-6 and the control non-digested samples were separated by 2-dimensional gel electrophoresis and the R-Csp-6-cleaved proteins were sequenced by LC/MS/MS. We found that Csp-6 cleaves one protein involved in intracellular signal transduction, three chaperone proteins, three proteins implicated in memory and learning, one protein involved in membrane fusion and vesicle transport, two proteins involved in neurotransmission, two cytoskeleton proteins and eight proteins that regulate actin, of which several regulate neuronal receptors and synapses. Putative Csp-6 substrates thus identified are being verified by in vitro and in vivo assays. The results indicate that early activation of Csp-6 in MCI and AD could alter cytoskeletal integrity resulting in memory and learning deficits.
Supported by FRSQ, CIHR MOP 15118 and McGill Dawson Award 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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