A common ingredient in many anti-aging potions may do more than help erase wrinkles. Kinetin may also slow or stop the effects of Parkinson’s disease on brain cells. The findings are published in the August 15, 2013 issue of Cell.

Nearly one million people in the US have Parkinson’s disease, a chronic and progressive movement disorder.

Researchers from Howard Hughes Medical Institute (HHMI) previously discovered mutations in a protein called PINK1 that were associated with the inherited form of Parkinson’s disease. Since then, studies have shown that PINK1 normally wedges into the membrane of damaged mitochondria inside cells that causes another protein, Parkin, to be recruited to the mitochondria, which are organelles responsible for energy generation. Neurons require high levels of energy production. Therefore, when mitochondrial damage occurs, it can lead to neuronal death.

However, when Parkin is present on damaged mitochondria, studding the mitochondrial surface, the cell is able to survive the damage. In people who inherit mutations in PINK1, however, Parkin is never recruited to the organelles, leading to more frequent neuronal death than usual. Shokat and colleagues wanted to develop a way to turn on or crank up PINK1 activity, therefore preventing an excess of cell death in those with inherited Parkinson’s disease, but turning on activity of a mutant enzyme is typically more difficult than blocking activity of an overactive version.

“When we started this project, we really thought that there would be no conceivable way to make something that directly turns on the enzyme,” says HHMI investigator and study author Kevan M. Shokat, PhD, of the University of California, San Francisco, in a news release. “For any enzyme we know that causes a disease, we have ways to make inhibitors but no real ways to turn up activity.”

To more fully understand how PINK1 works, the team began investigating how PINK1 binds to ATP, the energy molecule that normally turns it on. In one test, instead of adding ATP to the enzymes, they added different ATP analogues, versions of ATP with altered chemical groups that slightly change its shape. Scientists typically must engineer new versions of proteins to be able to accept these analogs, since they don’t fit into the typical ATP binding site. But one of the analogs—kinetin triphosphate, or KTP—turned on the activity of not only normal PINK1, but also the mutated version, which doesn’t bind ATP.

“This drug does something that chemically we just never thought was possible,” Shokat says. To test whether the binding of KTP to PINK1 led to the same consequences as the usual ATP binding, Shokat’s group measured the activity of PINK1 directly, as well as the downstream consequences of this activity, including the amount of Parkin recruited to the mitochondrial surface, and the levels of cell death. Adding the precursor of KTP, kinetin, to cells—both those with PINK1 mutations and those with normal physiology—amplified the activity of PINK1, increased the level of Parkin on damaged mitochondria, and decreased levels of neuron death, they found.

“What we have here is a case where the molecular target has been shown to be important to Parkinson’s in human genetic studies, and now we have a drug that specifically acts on this target and reverses the cellular causes of the disease.”

The similar results in cells with and without PINK1 mutations suggest that kinetin, which is a precursor to KTP, could be used to treat not only Parkinson’s patients with a known PINK1 mutation, but to slow progression of the disease in those without a family history by decreasing cell death.