کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
329540 | 1433667 | 2006 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Aβ in distal axons Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Aβ in distal axons](/preview/png/329540.png)
The goal of this study was to assess if neurons exposed to amyloid-β peptide (Aβ) exclusively in distal axons, undergo apoptosis. This is relevant to the loss of cholinergic neurons in Alzheimer's disease.Using a three-compartmented culture system for rat sympathetic neurons, we demonstrate that exposure of axons to Aβ1–42 activates an independent destruction program in axons, which leads to nuclear apoptosis. Aβ-induced axonal degeneration does not involve local caspase activation, but causes caspase activation in cell bodies. Accordingly, inhibition of caspase activation blocks Aβ-induced apoptosis but not axonal degeneration.In agreement with previous suggestions that disruption of nerve growth factor (NGF)-mediated signaling might contribute to the loss of cholinergic neurons, we found that provision of NGF to cell bodies protects sympathetic neurons from Aβ-induced apoptosis. However, our data indicate that Aβ-induced axonal degeneration follows a mechanism different than that activated by NGF withdrawal. Only Aβ-induced axonal degeneration is prevented by the calpain inhibitor calpastatin and is insensitive to the inhibitor of the ubiquitin–proteasome system MG132. Importantly, inhibition of Aβ-induced axonal degeneration by calpastatin prevents nuclear apoptosis.
Journal: Neurobiology of Aging - Volume 27, Issue 9, September 2006, Pages 1224–1238