Bidirectional regulation of Aβ levels by Presenilin 1
Abstract
Alzheimer’s disease is the most common neurodegenerative disorder, affecting more than 5 million people in the United States. Multiple lines of evidence suggest that the accumulation of toxic oligomers and aggregates of β-amyloid (Aβ) peptide are the primary causes of neurodegeneration. Aβ originates from sequential cleavage of the amyloid precursor protein (APP). The APP first cleavage is by β-secretase and yields β-C-terminal fragment (βCTF). In turn, βCTF is cleaved by Presenilin 1 (PS1) to produce Aβ. In this work, we show that PS1, in addition to generating Aβ, can also decrease Aβ levels by directing βCTF degradation through autophagy. This previously unrecognized mechanism of regulation of Aβ by Presenilin 1 could provide an attractive target for potential Alzheimer’s disease therapies.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 22, 2017
- Source ID
- 10.1073/pnas.1705235114
Entities
People
- Fred S. Gorelick
- Marc Flajolet
- Maria V. Pulina
- Paul Greengard
- Subhash C Sinha
- Victor Bustos
- Yildiz Kelahmetoglu
Organizations
- Fisher Center for Alzheimer's Research Foundation
- Freedom Together Foundation
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health
- The Rockefeller University
- United States Department of Defense
- Yale University