$3.9 million grant will explore role of brain enzymes in Alzheimer’s disease

Ying Xu, MD, PhD, research associate professor of pharmaceutical sciences, has received a $3.9 million grant from the National Institutes of Health National Institute on Aging to deepen the understanding of how phosphodiesterases (PDEs), in particular PDE2A, regulate cognition.

The research project, titled “Role of PDE2A in mitochondrial dysfunction in Alzheimer’s disease,” will run through April 2026.

PDEs are a superfamily of enzymes responsible for the regulation of important cellular functions. They are highly expressed in regions of the brain vulnerable to AD.

Preliminary studies found that overexpression of PDE2A impaired mitochondrial function accompanied by extensive mitochondrial fragmentation.

Xu’s study will provide mechanistic insights into molecular mechanisms underlying mitochondrial dysfunction in AD and deepen understanding of PDE2A in the regulation of cognition by the brain.

“The successful completion of this study will likely pave the way for future drug development of PDE2A inhibitors, specifically for the mitochondrial PDE2A2 isoform, as a promising treatment for Alzheimer’s disease,” says James M. O’Donnell, PhD, professor of pharmaceutical sciences.

Xu is also part of a Phase 2 clinical trial for a drug that may protect against memory loss, nerve damage and other symptoms of Alzheimer’s disease.