2011 Grants - Liao

Novel Regulation of BACE1 by Nitrosative and Metabolic Stresses

Francesca-Fang Liao, Ph.D.
University of Tennessee Health Science Center
Memphis, Tennessee

2011 Investigator-Initiated Research Grant

BACE1 (beta-secretase 1) is an enzyme thought to play a key role in Alzheimer's disease. BACE1 performs a critical step in the production of beta-amyloid, a protein fragment that aggregates into amyloid plaque, a characteristic feature of Alzheimer's pathology. Because of the importance of BACE1 in this process, its regulation is of great interest to scientists searching for ways to inhibit the production of beta-amyloid.

Francesca-Fang Liao, Ph.D. and colleagues have been studying how BACE1 is regulated in nerve cells. They have found preliminary evidence that BACE1 is regulated by energy- releasing processes as well as by several signaling systems, including those involved in the control of energy metabolism. One key signaling network thought to regulate BACE1 is known as the AMPK/SIRT/PGC-1 signaling network. Dysfunction of this network has also been implicated in type 2 diabetes, and it is thought to be affected by another signaling pathway involving the chemical nitric oxide.

Dr. Liao and colleagues have proposed to study how nitric oxide and the AMPK/SIRT/PGC-1 signaling network regulate the expression and activity of BACE1. These studies will provide important new insights into the regulation of BACE1 and the production of beta-amyloid, potentially identifying new targets for treatments to reduce the production of beta-amyloid and slow the progression of Alzheimer's pathology.