Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer's disease.

ABSTRACT: Dysregulation of autophagy, a cellular catabolic mechanism essential for degradation of misfolded proteins, has been implicated in multiple neurodegenerative diseases. However, the mechanisms that lead to the autophagy dysfunction are still not clear. Based on the results of a genome-wide screen, we show that reactive oxygen species (ROS) serve as common mediators upstream of the activation of the type III PI3 kinase, which is critical for the initiation of autophagy. Furthermore, ROS play an essential function in the induction of the type III PI3 kinase and autophagy in response to amyloid beta peptide, the main pathogenic mediator of Alzheimer's disease (AD). However, lysosomal blockage also caused by Abeta is independent of ROS. In addition, we demonstrate that autophagy is transcriptio

SUBMITTER: Lipinski MM 

PROVIDER: S-EPMC2922576 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature