Brain receptor cell could be target for Alzheimer's treatment, study says

Scientists believe blocking a key receptor in brain cells may play a major role in diffusing the biological consequences of Alzheimer’s disease, according to a new study.

The research, published in the journal Neurobiology of Aging, analyzed the human body’s use of oxygen to produce energy, which can result in the formation of highly reactive molecules called oxygen-free radicals. Oxidative stress can also occur when the production of these free radicals is greater than the body’s ability to detoxify them.

“Besides the two major signature brain pathologies associated with Alzheimer’s disease, amyloid beta plaques and the tangles which are formed from the phosphorylation of the tau protein, researchers have also known for a while that there is a signature from oxidation stress,” Domenico Pratico, study lead and professor of pharmacology and microbiology and immunology at Temple University, said in a news release.

“But it has always been believed that oxidative stress was just a bystander and did not have an active function in the development of the disease,” Pratico said.

Using a mouse model of Alzheimer’s, researchers introduced free radicals into the brain and noted a decline in memory and learning capabilities, as well as an increase in amyloid beta and tangles.

The team discovered that the free radicals produced during oxidative stress bind to a protein receptor in the brain called thromboxane reception (TP), and transmit signals to the neuronal cells to increase the production of amyloid beta or phosphorylated tau.

“Basically it sends the wrong message inside the neuronal cells, and with time, this definitely will result in all the clinical manifestations of the disease, such as cognitive impairment, loss of memory and brain cell death,” Pratico said.

In another group of mice, the researchers added a compound that blocks the TP receptor in the brain, and they found there was no manifestation of the cognitive impairment, according to the news release.

“This indirectly confirmed for us that the free radicals worked through this receptor,” Pratico said. “Using this compound, we were able to completely neutralize the biological consequences of the free radicals in terms of the amyloid beta production (plaques) and tau phosphorylation (tangles).”

The team believes their research can help improve therapy, as their findings suggest targeting the TP may prove effective in treatment for Alzheimer’s patients. The researchers are working on developing additional compounds to efficiently block to the receptor.