Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Abeta in distal axons. Export

@article{citeulike:3270164, abstract = {The goal of this study was to assess if neurons exposed to amyloid-beta peptide (Abeta) 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 Abeta1-42 activates an independent destruction program in axons, which leads to nuclear apoptosis. Abeta-induced axonal degeneration does not involve local caspase activation, but causes caspase activation in cell bodies. Accordingly, inhibition of caspase activation blocks Abeta-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 Abeta-induced apoptosis. However, our data indicate that Abeta-induced axonal degeneration follows a mechanism different than that activated by NGF withdrawal. Only Abeta-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 Abeta-induced axonal degeneration by calpastatin prevents nuclear apoptosis.}, address = {Centre for Alzheimer and Neurodegenerative Research, Signal Transduction Research Group and Department of Pharmacology, 928 Medical Science Building, Faculty of Medicine, University of Alberta, Edmonton, Alta., Canada T6G 2H7.}, author = {Song, M. S. and Saavedra, L. and de Chaves, E. I.}, citeulike-article-id = {3270164}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.neurobiolaging.2005.06.007}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16122841}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16122841}, doi = {10.1016/j.neurobiolaging.2005.06.007}, issn = {1558-1497}, journal = {Neurobiology of aging}, keywords = {alzheimers, axonal, compartmental, degeneration}, month = {September}, number = {9}, pages = {1224--1238}, posted-at = {2008-09-15 17:09:18}, priority = {0}, title = {Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Abeta in distal axons.}, url = {http://dx.doi.org/10.1016/j.neurobiolaging.2005.06.007}, volume = {27}, year = {2006} }

TY - JOUR ID - citeulike:3270164 L3 - citeulike-article-id:3270164 N2 - The goal of this study was to assess if neurons exposed to amyloid-beta peptide (Abeta) 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 Abeta1-42 activates an independent destruction program in axons, which leads to nuclear apoptosis. Abeta-induced axonal degeneration does not involve local caspase activation, but causes caspase activation in cell bodies. Accordingly, inhibition of caspase activation blocks Abeta-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 Abeta-induced apoptosis. However, our data indicate that Abeta-induced axonal degeneration follows a mechanism different than that activated by NGF withdrawal. Only Abeta-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 Abeta-induced axonal degeneration by calpastatin prevents nuclear apoptosis. IS - 9 JF - Neurobiology of aging SN - 1558-1497 AD - Centre for Alzheimer and Neurodegenerative Research, Signal Transduction Research Group and Department of Pharmacology, 928 Medical Science Building, Faculty of Medicine, University of Alberta, Edmonton, Alta., Canada T6G 2H7. EP - 1238 TI - Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Abeta in distal axons. VL - 27 SP - 1224 KW - alzheimers KW - axonal KW - compartmental KW - degeneration AU - Song, MS AU - Saavedra, L AU - de Chaves, EI PY - 2006/09// UR - http://dx.doi.org/10.1016/j.neurobiolaging.2005.06.007 ER -