UB receives $3.9 million grant to better understand role of brain enzymes in early stages of Alzheimer’s disease

BUFFALO, N.Y. – To better understand the molecular dysfunctions underlying Alzheimer’s disease, University at Buffalo researcher Ying Xu has received a $3.9 million grant from the National Institute on Aging to examine the role of phosphodiesterases (PDEs) in cognition and behavior. 

PDEs are a superfamily of enzymes that regulate molecules critical to important bodily functions, including memory and mood. Preliminary studies found that one form located exclusively in the mitochondria, PDE2A2, is highly expressed in the brains of Alzheimer’s disease patients, impairing mitochondrial function in neurons.

Although mitochondrial dysfunction in neurons may be an early sign of Alzheimer’s disease, the underlying molecular mechanisms remain a mystery, says Xu, MD, PhD, research associate professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences. 

“Our past research has demonstrated the cognitive-enhancing effect of PDE2A inhibitors,” says Xu, who is also a co-investigator on a research collaboration between UB and Tetra Therapeutics to develop and test a new drug that may protect against memory loss, nerve damage and other symptoms of Alzheimer’s disease.

“The successful completion of this study will likely pave the way for future drug discovery for PDE2A inhibitors as promising treatments for Alzheimer's disease or other neuropsychiatric illnesses,” she says.

James M. O’Donnell, PhD, professor of pharmaceutical sciences in the UB School of Pharmacy and Pharmaceutical Sciences, is a co-investigator on the five-year study.