"I call JAK2 the good, the bad and the ugly because its function depends on the cell type and where it acts," says the biochemist at the Medical College of Georgia who wants to eliminate or at least control the "bad" and "ugly."
JAK2, or janus kinase 2, is an enzyme found in all cells that plays an important role in development and growth; mice lacking this enzyme die in utero, Dr. Marrero says. After birth, the enzyme becomes a two-edged sword that activates or deactivates other proteins and plays a role in Alzheimer's, diabetes, hypertension and kidney failure.
When JAK2 is good, it helps protect brain cells from Alzheimer's disease by blocking the action of amyloid-b peptide, the plaque-producing protein fragment implicated in Alzheimer's disease.
Nicotine, long known to have a neuro-protective role despite its other drawbacks, apparently uses JAK2 to enable this protection. "When brain cells are exposed to beta amyloid that makes plaque, nicotine protects them by activating JAK2, which activates a pathway of cell survival and blocks the beta activation of the pathway that leads to cell death," says Dr. Marrero, who discovered nicotine's ability to regulate JAK2 in collaboration with Dr. Merouane Bencherif, vice president of preclinical research at the North Carolina-based pharmaceutical company, Targacept, Inc.
But if angiotensin II a powerful vasoconstrictor involved in blood pressure regulation and a growth factor as well is added to the mix, nicotine no longer protects brain cells. "Angiotensin II doesn't allow JAK2 to be activated by nicotine," Dr. Marrero says.
This finding supports his theory that nicotine protects neurons through the JAK2 pathway but also points toward new treatment approaches for Alzheimer's and
Contact: Toni Baker
Medical College of Georgia