June 2, 2006

Free radical mechanism found

Scientists at Harvard Medical School have found a mechanism behind the damage that oxidative stress causes to cells which results in the deterioration associated with aging and disease. Oxidative stress is caused by highly reactive molecules known as free radicals formed as a byproduct of metabolism. Although free radicals are quenched by antioxidants, the increase in free radical production that occurs with age overwhelms the body's antioxidant defenses, resulting in damage to the cells' DNA, proteins and lipids. The findings were published in the June 1, 2006 issue of the journal Cell.

Azad Bonni, MD, PhD and colleagues discovered that exposure of brain neurons to oxidative stress signals caused by free radicals stimulates the activity of an enzyme called MST, which previous research had determined to be involved in cell death. They also found that once MST is stimulated by oxidative stress, it activates another family of molecules known as FOXO proteins, instructing them to move from the cells' cytoplasm (the body of the cell) into the cell nucleus. The researchers discovered that when FOXO enters the nucleus, it switches on genes that instruct neurons to self-destruct.

"A common molecular denominator in aging and many age-related diseases is oxidative stress," observed Dr Bonni, who is the lead author of the report and an associate professor of pathology at Harvard Medical School. Discovery of the MST-FOXO mechanism is an important piece of information in defining how oxidative stress causes a biological response in neurons. Because oxidative stress in neurons and other cells has been implicated in stroke, heart disease, diabetes, and neurodegenerative and other disorders, the FOXO mechanism could become a target for therapies for these diseases.