Researchers at the University of California, Irvine have identified a combination of naturally occurring compounds that may help rejuvenate aging brain cells and remove harmful proteins linked to Alzheimer’s disease. The study, published in GeroScience, found that nicotinamide (a form of vitamin B3) and epigallocatechin gallate (an antioxidant from green tea) can restore levels of guanosine triphosphate (GTP), an energy molecule essential for brain cell function.
Lead author Gregory Brewer, adjunct professor of biomedical engineering at UC Irvine, explained the significance of these findings. “As people age, their brains show a decline in neuronal energy levels, which limits the ability to remove unwanted proteins and damaged components,” Brewer said. “We found that restoring energy levels helps neurons regain this critical cleanup function.”
The research team used a genetically encoded fluorescent sensor called GEVAL to monitor live GTP levels in neurons taken from aged mice bred to model Alzheimer’s disease. Their results showed that free GTP declined with age, especially in mitochondria—the cell’s main energy producers—which led to impaired autophagy, the process by which cells clear out damaged material.
Treatment with nicotinamide and epigallocatechin gallate for 24 hours restored GTP levels in older neurons to those seen in younger ones. This improvement also enhanced energy metabolism, activated key cellular trafficking proteins Rab7 and Arl8b, and promoted more effective removal of amyloid beta aggregates—a hallmark feature of Alzheimer’s disease. The researchers observed reduced oxidative stress as well.
“This study highlights GTP as a previously underappreciated energy source driving vital brain functions,” Brewer said. “By supplementing the brain’s energy systems with compounds that are already available as dietary supplements, we may have a new path toward treating age-related cognitive decline and Alzheimer’s disease.”
Brewer cautioned that further research is needed on how best to deliver this treatment: “More work is going to be required to find the best way to administer this treatment, since a recent clinical trial involving UC Irvine researchers showed that oral nicotinamide was not very effective because of inactivation in the bloodstream.”
Ricardo Santana and Joshua McWhirt contributed to the study. Funding came from the National Institutes of Health and the UC Irvine Foundation.
