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2007 Grant - Ma
Mechanisms of PTEN Signaling Defects in Alzheimer's Disease
Qiulan Ma, M.D., Ph.D.
Sepulveda Research Corporation
North Hills, California
2007 New Investigator Research Grant
Phosphate and tensin homolog (PTEN) is a protein inside of cells that is important in many signaling pathways (protein chains of command). For example, PTEN is critical for the function of many growth factors that maintain cell growth and survival. Studies have found that levels of PTEN are reduced in people with Alzheimer's disease, as well as in animal models that develop an Alzheimer-like pathology.
Qiulan Ma, M.D., Ph.D., and colleagues have preliminary evidence that PTEN signaling is disrupted by beta-amyloid, a protein fragment that forms the amyloid plaques characteristic of Alzheimer's disease. They plan to perform additional research to test this concept in mice, as well as to study the conse-quences of PTEN disruption, which may include damage to energy production in the cell and loss of synapses in the brain. Synapses are specialized regions of nerve cells that allow the cells to send and receive signals.
The researchers have also obtained preliminary evidence that an omega-3 fatty acid, DHA (docosahexaenoic acid), increases the activity of PTEN in mice, possibly counteracting the effects of beta-amyloid. DHA is already being studied in clinical trials of late-stage Alzheimer's disease, but Dr. Ma and colleagues plan to test in animal models whether it would be more likely to succeed as a treatment when used in early stages of the disease. These studies will provide valuable information about the possible function, and best use, of a drug that is already in clinical trials for the treatment of Alzheimer's disease.