Neurological researchers at Rush University Medical Center, in Chicago, claim to have found a "therapeutic target" that potentially could lead to a new way to prevent the progression of Alzheimer's disease.

The target, called neutral sphingomyelinase (N-SMase), is a protein that, when activated, can cause a chain reaction in the cell, leading to the death of neurons and memory loss.

Results from the study, which was funded by the National Institutes of Health and the Alzheimer's Association, were published last month in the medical journal Neuroscience.

"There are multiple, neurotoxic, disease-causing pathways that converge on the (protein) that can cause neuronal loss in the brain of an Alzheimer's patient," says Kalipada Pahan, lead investigator at Rush. "If we can stop the activation of the (protein), we may be able to stop memory loss and the progression of Alzheimer's disease."

In the brain of a patient with Alzheimer's disease, two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. While neurons die, other brain cells like astroglia and microglia don't die. These cells become activated, and that activation plays a key role in the destruction of neurons. However, the molecular mechanisms by which activated glial cells can kill neurons have been poorly understood until now.

Beta-amyloid, which is a protein fragment deposited in the brains of patients who have Alzheimer's disease, causes the activation of glial cells. When healthy nerve cells in the brain are exposed to beta-amyloid, they exhibit a number of pathological changes that are characteristic of Alzheimer's pathology.

Researchers were able to determine that the neutral sphingomyelinase is triggered by the activated brain cells and beta-amyloid. When the neutral sphingomyelinase was inhibited by using a small molecule inhibitor and a chemical inhibitor, the activated brain cells and beta amyloid were unable to kill neurons.

Experts tested the two inhibitors using human brain cells in a mouse model and a cell culture model.

"Understanding how the disease process works is important in identifying effective approaches to protect the brain and stop the progression of Alzheimer's disease," says Pahan. "The results of this study are very promising, and our next step is to translate these findings to the clinic."

"If we can develop and test a clinical medication that can target the neutral sphingomyelinase, we may be able to halt memory loss in Alzheimer's disease patients," Pahan says.