To view an abstract, select an author from the vertical list on the left.
2017 Grants - Krishnan
Inhibition of Phospholipase D1 as Therapeutic in AD-Related Memory Deficits
Balaji Krishnan, Ph.D.
University of Texas Medical Branch at Galveston
2017 Alzheimer’s Association Research Grant (AARG)
Does inhibition of the protein phospholipase D1 prevent or slow degeneration of synapses that occurs in Alzheimer’s disease?
One of the unique features of nerve cells is their ability to send and receive rapid signals to each other. This feature accounts for the brain’s ability to learn and remember, and is mediated by specialized structures known as synapses. In the early stages of Alzheimer’s disease, however, synapses begin to shrink and malfunction. Those changes may explain some of the loss of brain function and cognitive problems that occurs during disease onset.
Phospholipase D1 is a protein found in nerve cell synapses. Several lines of evidence suggest that over activity of phospholipase D1 may contribute to the degeneration of synapses in the early stages of Alzheimer’s disease.
Balaji Krishnan, Ph.D., and colleagues have proposed two types of studies to explore the role of phospholipase D1 in synapse degeneration and Alzheimer’s disease. For the first type of study, the researchers will obtain samples of tissue from autopsy specimens and use biochemical methods to measure the activity of phospholipase D1. The team will study how the activity of this protein changes in people who have mild cognitive impairment, a condition that sometimes precedes Alzheimer’s, and those that go on to develop Alzheimer’s disease.
For the second study, Dr. Krishnan and colleagues will use mice that have been genetically altered to have an Alzheimer’s-like condition. The researchers will treat the mice with a drug known to inhibit phospholipase D1, and then measure how such treatment affects the onset or progression of Alzheimer’s like changes in brain function and behavior.
These studies will explore a potential molecular mechanism of early changes to synapses in early stages of Alzheimer’s disease. The results will help scientists determine if drugs that inhibit phospholipase D1 should be studied further as possible treatments to prevent, slow or halt the progression of Alzheimer’s disease.