Endoplasmic reticulum plays important roles in initiating autophagy in cultured hippocampal neurons after exposure to beta-amyloid peptide

Abstract

BACKGROUND: Autophagy has long been considered to be one of the mechanisms for cells to clear damaged intracellular organelles. It has not been clear of how autophagy or formation of autophagic vacuoles is initiated in Alzheimer's disease (AD) or β-amyloid (Aβ) peptide neurotoxicity in neurons. We have reported that cultured neurons exposed to oligomeric Aβ peptide display aggregation and collapse of the endoplasmic reticulum (ER). This is due to the instability of microtubules leading to detachment of the ER from microtubules. Concomitantly, increase of autophagic vacuoles can be observed after aggregation of the ER. The aim of this study is to investigate molecular mechanisms of how aggregation of the ER initiates formation of auto…