Compound May Help Prevent Neuron Damage in Age-Related Diseases

A known compound called rapamycin has a newly-discovered mechanism that might help prevent neurologic damage in Alzheimer’s disease and other age-related conditions, according to a new study published in the journal Aging Cell.

“It’s possible this could provide a new therapeutic approach to neurologic disease,” said Viviana Perez, an assistant professor in the Department of Biochemistry and Biophysics at Oregon State University’s (OSU) College of Science, an expert on the biological processes of aging and principal investigator in the Linus Pauling Institute.

“The value of rapamycin is clearly linked to the issue of cellular senescence, a stage cells reach where they get old, stop proliferating, and begin to secrete damaging substances that lead to inflammation,” Perez said. “Rapamycin appears to help stop that process.”

This process creates a toxic environment called senescence-associated secretory phenotype (SASP). Researchers believe this action disrupts the cellular microenvironment and alters the ability of adjacent cells to function properly, compromising their tissue structure and function.

“The increase in cellular senescence associated with aging, and the inflammation associated with that, can help set the stage for a wide variety of degenerative disease, including cancer, heart disease, diabetes, and neurologic disease, such as dementia or Alzheimer’s,” Perez said.

“In laboratory animals when we clear out senescent cells, they live longer and have fewer diseases. And rapamycin can have similar effects.”

Rapamycin is a natural compound first discovered from the soils of Easter Island in the South Pacific Ocean. It has already been intensively studied because it can mimic the valuable effects of dietary restriction, which in some animals has been shown to extend their lifespan.

In fact, laboratory mice that have received rapamycin have demonstrated more stamina, less decline in activity with age, improved cognition, and cardiovascular health, less cancer, and a longer life.

Prior to this research, only one mechanism of action had been observed for rapamycin. Scientists believed it helped to increase the action of Nrf2, a master regulator that can “turn on” up to 200 genes responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other factors. In the process, it helped reduce levels of SASP.

In the new study, the researchers found that rapamycin could also affect levels of SASP directly, separately from the Nrf2 pathway and in a way that would have impacts on neurons as well as other types of cells.

“Any new approach to help protect neurons from damage could be valuable,” Perez said. “Other studies, for instance, have shown that astrocyte cells that help protect neuron function and health can be damaged by SASP. This may be one of the causes of some neurologic diseases, including Alzheimer’s disease.”

Rapamycin will continue to generate significant interest in addressing issues related to aging, Perez said. One drawback, however, is that the use of rapamycin in humans has been halted by a negative side effect — an increase in insulin resistance that may raise the risk of diabetes.

This concern still exists and limits the use of rapamycin to help address degenerative disease until ways can be found to address that problem. Scientists are currently searching for rapamycin analogs that may have similar biological impacts but don’t cause that unwanted side effect.

Source: Oregon State University