New target identified for Alzheimer’s disease

September 29, 2010

Neurological researchers at Rush University Medical Center have found a new therapeutic target that can potentially 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 of reactions in the cell leading to neuronal death and memory loss.

Results from the study funded by the National Institutes of Health and the Alzheimer’s Association will be published in the September 22 issue of the .

“There are multiple, neurotoxic, disease-causing pathways that converge on the neutral sphingomyelinase that can cause neuronal loss in the brain of an Alzheimer’s patient,” said Kalipada Pahan, PhD, neurological researcher and lead investigator at Rush. “If we can stop the activation of the neutral sphingomyelinase, 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 . While neurons die, other brain cells like astroglia and microglia do not die. These brain cells become activated, and the glial cell 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. Neuritic plaques are mainly composed of aggregates of beta-amyloid. 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 at Rush were able to determine that the neutral sphingomyelinase is triggered by the activated brain cells and beta-amyloid. However, 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 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,” said 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,” said Pahan.

Alzheimer's disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimer's, symptoms first appear after age 60. Alzheimer's disease is the most common cause of dementia among older people. affects as many as 5.3 million Americans.

Related Stories

Recommended for you

Researchers make surprising discovery about how neurons talk to each other

August 17, 2017
Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge ...

How we recall the past: Neuroscientists discover a brain circuit dedicated to retrieving memories

August 17, 2017
When we have a new experience, the memory of that event is stored in a neural circuit that connects several parts of the hippocampus and other brain structures. Each cluster of neurons may store different aspects of the memory, ...

Researchers show how particular fear memories can be erased

August 17, 2017
Researchers at the University of California, Riverside have devised a method to selectively erase particular fear memories by weakening the connections between the nerve cells (neurons) involved in forming these memories.

Neurons involved in learning, memory preservation less stable, more flexible than once thought

August 17, 2017
The human brain has a region of cells responsible for linking sensory cues to actions and behaviors and cataloging the link as a memory. Cells that form these links have been deemed highly stable and fixed.

Study uncovers specialized mouse neurons that play a unique role in pain

August 17, 2017
Researchers from the National Institutes of Health have identified a class of sensory neurons (nerve cells that electrically send and receive messages between the body and brain) that can be activated by stimuli as precise ...

Scientists identify central neural circuit for itch sensation

August 17, 2017
Itching is an unpleasant sensation associated with the desire to scratch, and the itch sensation is an important protective mechanism for animals. However, chronic itch, often seen in patients with skin and liver diseases, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.