Researchers at the University of Colorado Anschutz Medical Campus have found that inhibiting a key protein can prevent the destruction of synapses and dendritic spines commonly seen in Alzheimer’s disease.

The study, first authored by Tyler Martinez, a student in the pharmacology and molecular medicine PhD program at the University of Colorado School of Medicine, was recently published in the journal eNeuro

The researchers, using rat neurons, found that targeting a protein called Mdm2 with an experimental cancer drug known as nutlin blocked the neurotoxic amyloid-B peptides that cause Alzheimer’s disease ( AD) accumulates in synapses from most pruning.

“Cognitive impairments associated with AD are associated with loss of dendritic spines and excitatory synapses,” said senior study author Professor Mark Del Acqua, PhD, vice chair of the Department of Pharmacology at the CU School of Medicine. are.”

The pruning of additional dendritic spine synapses is normal in the postnatal brain but may be abnormally accelerated in AD, leading to memory and learning deficits, Dell’Acqua said.

“When this protein Mdm2 is turned on inappropriately, it causes the pruning of synapses when amyloid-b is present,” he said. Amyloid-b is the main component of amyloid plaques found in the brains of people with AD. “When we used a drug that inhibits Mdm2 on neurons, it completely blocked the loss of dendritic spines caused by amyloid-b. So blocking this protein is clearly working. “

Dendritic spines arise from dendrites, a component of neurons, and receive synaptic signals that are important in learning and memory.

Del Acqua, director of the Neurotechnology Center at the CU School of Medicine, noted that much of the research into treating AD has focused on eliminating amyloid plaques in the brain.

“There are questions as to whether anti-amyloid therapy ends all AD therapy,” he said. “Even if you can afford the high cost, the effectiveness is questionable. We’re saying that it may be possible to interfere with the process by blocking some of the effects of amyloid-B. And you can interfere by targeting Mdm2. “

The next step is determining whether they can prevent AD progression in animal models. If so, human trials may be possible in the future. Drugs targeting Mdm2 are already in development and in clinical trials for cancer but still require FDA approval.

“This is an encouraging first step that gives us new leadership to move forward,” Del Acqua said.