Please use this identifier to cite or link to this item: http://dl.umsu.ac.ir/handle/10722/146946
Title: Aggregation of the endoplasmic reticulum may play a major role in initiating autophagic flux in oligomeric β-amyloid peptide-treated neurons
Authors: Ho, YS;Wuwongse, S;Zhang, NQ;Hung, CHL;Chang, RCC
subject: Endoplasmic reticulum;Autophagy;Amyloid
Year: 2011
Publisher: Society for Neuroscience.
United States
Description: Nanosymposium - 637. Alzheimer's Disease and Other Dementias: Abeta Oligomerization and Toxicity: Poster no. 637.10
Increasing lines of evidence have shown that autophagy can be an adaptive process for neurons to struggle for survives. Our previous studies have demonstrated the presence of autophagosomes in concomitance with the aggregation of the endoplasmic reticulum (ER) in cultured neurons upon exposure to oligomeric β-amyloid (Aβ) peptide. However, the precise mechanisms of how aggregation of the ER leads to formation of autophagosomes are largely unclear. We hypothesize that the damaged ER serves as a seed for nucleation proteins to form autophagosomes. The aim of this study is to elucidate the biological mechanisms of the nucleation step. Primary cultures of hippocampal neurons were employed for this study. Different DNA constructs conjugated with fluorescent proteins were used to monitor the change of autophagic flux in live neurons. By using multiphoton live cell imaging system, we observed that Aβ-induced autophagosomes were accompanied by omegasomes which were precursors for autophagosomes. Aggregation of the ER could facilitate the formation of the omegasomes. Meanwhile, Atg14L, a key mediator for forming omegasomes, was also found to be clustered at the ER aggregation site. The clustered Atg14L would further recruit Beclin 1-Vps34 to form a nucleation complex that would contribute to formation of omegasomes. Our results are among the first to demonstrate how aggregated ER trigger autophagy in neurons stressed by oligomeric Aβ peptide.
URI: http://hub.hku.hk/handle/10722/146946
Standard no: The 41st Annual Meeting of the Society for Neuroscience (SfN 2011), Washington, D.C., 12-16 November 2011.
199441
Appears in Collections:Department of Anatomy

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