To view an abstract, select an author from the vertical list on the left.
2007 Grant - Gama Sosa
Presenilin-1 and Signaling Through the HIF Pathway
Miguel A. Gama Sosa, Ph.D.
Mount Sinai School of Medicine
Bronx, New York
2007 Investigator-Initiated Research Grant
Presenilin-1 is a protein that has been of great interest to researchers studying Alzheimer's disease, because the gene for presenilin-1 is mutated in many persons who have inherited forms of the disease. How mutations of the presenilin-1 gene lead to Alzheimer's disease is not well understood, but it has been observed that such mutations lead to greater production of beta-amyloid, a protein fragment that accumulates in the Alzheimer brain and is toxic to brain cells.
Gama Sosa, Ph.D., and colleagues have observed that mice with mutations in the presenilin-1 gene show abnormal expression of another protein known as HIF1a. HIF1a is a very important protein that controls a cell's ability to respond to numerous signals, especially signals controlling cell growth and metabolism. One of the signals that may rely on HIF1a is insulin. Thus, the researchers have suggested that abnormal expression of HIF1a may impair the ability of brain cells to respond to insulin, which in turn would impair the cells' ability to survive, grow, and interact with other cells.
Because cells in the brains of people with Alzheimer's have many of the same impairments as those in cells with presenilin-1 mutations (and abnormal expression of HIF1a), Dr. Gama Sosa and colleagues have proposed to study this signaling system and how it is altered in mice with genetic alterations that mimic Alzheimer's disease. Their studies may help to identify new drug targets that could be used to treat the disease.