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2011 Grants - Frenkel
The Role of Specific Gamma-Secretase Pathways in Microglia Activation
Dan Frenkel, Ph.D.
Tel Aviv University
Tel Aviv, Israel
2011 New Investigator Research Grant
The protein fragment beta-amyloid, a key suspect in Alzheimer's disease, is produced from a parent molecule called amyloid precursor protein (APP). One of the proteins that cleaves beta-amyloid from APP is gamma-secretase. Yet gamma-secretase also helps produce other proteins essential for brain health. Another factor in the early development of Alzheimer's involves helper cells called microglia. These immune system cells may become abnormally produced and activated during early dementia.
Dan Frenkel, Ph.D., and colleagues speculate that gamma-secretase and microglial cells may work together in promoting brain disease. Gamma-secretase cleaves proteins that play a role in microglial activation, and an Alzheimer's-related genetic mutation may cause gamma-secretase to promote both microglial dysfunction and the increased production of beta-amyloid. The researchers hypothesize that by modifying this toxic chain of molecular activities, they may be able to prevent the onset of Alzheimer's disease.
For their grant, Dr. Frenkel and colleagues will use genetic techniques to study different ways that gamma-secretase may affect the activity of microglial cells. By identifying the precise biological links between gamma-secretase and microglia, the team hopes to reveal techniques for moderating disease-related microglial activation. Such work could also identify gamma-secretase-induced microglial functions that may prove beneficial to brain health.