Franco Lab

Maria Clara “Maca” Franco, center, with Kyle Nguyen, left, and Lydia Bastian. Franco’s research investigates neurodegenerative diseases. Image courtesy of Oregon State University.

Researchers at Oregon State University (OSU) have discovered a new class of potential drug targets for diseases like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS).

The scientists are working to identify the best method to attack the targets — oxidized proteins. The most potent oxidant of the bunch is peroxynitrite, which is produced in conditions involving inflammation. Oxidized proteins and free radicals can damage DNA, lipids and proteins implicated in neurodegenerative diseases and other conditions.

Peroxynitrite is produced thanks to the diffusion-limited reaction of nitric oxide and superoxide.

Peroxynitrite appears to be especially pernicious when it oxidizes heat shock protein 90 (Hsp90), leading to signal activation that results in apoptosis or cell death.

The peroxynitrite ion plays a role in neuronal death in various central nervous system conditions such as stroke, multiple sclerosis and spinal cord injury.

“Now we know that the oxidation of different parts of Hsp90 can elicit different toxic functions in the protein,” said Maria Clara Franco, an assistant professor at OSU.

“By understanding the ways that oxidation modifies the Hsp90 structure and how the oxidized protein works in the cells, we can look for drugs that bind to the modified structure of Hsp90 and stop its toxic function without affecting the activity of normal Hsp90 in healthy tissues,” Franco said in a statement. “That means such drugs should have minimal to no side effects.”

The researchers had concluded that peroxynitrite was implicated in the death of motor neurons.

Their research was published in Redox Biology.