Hope for Treating Alzheimer’s Progression
A promising new therapeutic target has been identified that could open doors to preventing the progression of Alzheimer’s disease.
A study completed at Rush University Medical Center found that when activated, the protein neutral sphingomyelinase (N-SMase) can cause a chain of reactions in cells leading to neuronal death and memory loss.
“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, lead author of the new study.
“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.”
Two abnormal structures called plaques and tangles have previously been identified as agents involved in damaging and killing nerve cells in Alzheimer’s patients. While scientists have not been certain about the role plaques and tangles play, many experts believe they block communication among nerve cells and disrupt activities needed for cell survival.
Specifically, plaques build up between nerve cells and contain deposits of a protein fragment called beta-amyloid. Beta-amyloid is deposited in the brains of patients who have Alzheimer’s disease and cause 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 said that glial cell activation plays a key role in the destruction of neurons, but until now, the molecular mechanisms by which activated glial cells can kill neurons have been poorly understood.
This study’s discovery of neutral sphingomylinase is important to future progress in treating Alzheimer’s in that it identifies the protein that is triggered by the activated brain cells and beta-amyloid.
Researchers also found that a small molecule inhibitor and chemical inhibitor used on the neutral sphingomyelinase could eliminate the ability of the activated brain cells and beta amyloid 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,” said Pahan. “The results of this study are very promising and our next step is to translate these findings to the clinic.”
Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills. A progressively debilitating disease, the effects eventually impact a person’s 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 and affects as many as 5.3 million Americans.
“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.
Results from the study will be published in the Sept. 22 issue of the Journal of Neuroscience.
Source: Rush University Medical Center
Chavis, S. (2015). Hope for Treating Alzheimer’s Progression. Psych Central. Retrieved on March 20, 2018, from https://psychcentral.com/news/2010/09/25/hope-for-treating-alzheimers-progression/18662.html