Tiny protein prevents disease-related cell death

Tiny protein targets Bax, inhibits apoptosis

Researchers at The Burnham Institute have found that humanin, a small, 24-amino acid protein recently discovered in studies of Alzheimer’s Disease, suppresses activation of the protein Bax. Bax triggers pathologic cell death in a number of diseases, including Parkinson’s, stroke, heart attack and degeneration of ovaries during menopause. These results, to be published later this month in the journal Nature (currently available at the journal’s website), suggest a novel target for therapeutic design based on inhibiting the cell destructive activity of Bax.

Bax protein is known to promote the cell death program (also known as apoptosis) latent in all cells. It does so by attacking the cell’s powerhouse, called “mitochondria”, resulting in the cell’s demise. Apoptosis is critical for normal development and maintaining cell balance. Many diseases are identified with malfunction of apoptosis: too much cell death is associated with degenerative diseases of the nervous system, stroke and heart attack; failure to activate the cell death program is one of the hallmarks of cancer.

Dr. Reed’s laboratory identified humanin as a Bax-interactive protein. In the current study, they showed that humanin bound to Bax, which prevented its targeting to mitochondria and blocked its ability to cause cell death.

“Our results demonstrate that Bax is the target of humanin, and they suggest at least three novel ways of designing therapeutics that could prevent or arrest diseases associated with activation of Bax,” says Dr. Reed.

Dr. Reed envisions that the tiny protein humanin could be synthesized and developed as an injectable drug for acute situations, such as heart attack or stroke, because humanin has the unique ability to readily enter cells. Gene therapy that exploits humanin’s ability to translocate from cell to cell could also be developed to protect cells in the vicinity of the gene’s injection, such as the heart or certain regions of the brain. Structural information about humanin could be used to pattern chemicals developed into pill form, for more convenient administration protecting against pathological cell death.

Dr. Reed is President and CEO of The Burnham Institute, and Professor in the Institute’s Del E. Webb Center for Neuroscience and Aging Research and in the Cancer Center.

Co-author Arnold Satterthwait, Ph.D., Burnham Institute Professor, synthesized peptides used in this study.

This research was supported by grants from the National Institutes of Health, and the Department of Defense.

The Burnham Institute is an independent, nonprofit, public benefit organization dedicated to basic biomedical research principally in the areas of cancer, aging, and the neurosciences. The Institute ranks consistently among the world’s most influential research organizations for the impact of its research in analyses conducted annually by the Institute for Scientific Information.