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2011 Grants - Bruno
PDE4D Selective Inhibitors for the Treatment of Memory Impairment
Olga Bruno, Ph.D.
University of Genoa
2011 Investigator-Initiated Research Grant
Learning and memory involves the activity of numerous signaling pathways in the brain, operating both inside and outside of nerve cells. Each pathway consists of a complex chain of molecules involved in generating, transmitting and regulating the flow of signals. PDE4D (phosphodiesterase 4D) is an enzyme that regulates one important signaling pathway inside nerve cells by breaking down a key signaling molecule known as cyclic AMP. Cyclic AMP is known to be important in some instances of memory formation.
Olga Bruno, Ph.D. and colleagues from several teams of researchers are using a variety of scientific approaches in an effort to develop drugs that selectively inhibit PDE4D. The goal of this research is to develop a drug candidate that improves memory in persons with memory impairment caused by Alzheimer's disease.
Dr. Bruno's team will use biochemical methods to develop several candidate drugs that bind to and inhibit PDE4D without causing toxicity to brain cells. Researchers collaborating with Dr. Bruno's team will test whether these drug candidates affect the development of Alzheimer-like pathology. Another group of collaborators will test whether the drug candidates improve the function of brain synapses, specialized devices that allow nerve cells to send rapid signals through the brain and which are crucial for learning and memory. Using mice that have been genetically altered to express Alzheimer-like pathology, the researchers will test whether PDE4D inhibitors can restore the ability of synapses to perform memory functions. They will also test whether these drug candidates improve the ability of the mice to perform behavioral tasks requiring memory. These studies may lead to the development of drug candidates for the treatment of memory impairments in persons with Alzheimer's disease.