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2011 Grants - Georgakopoulos
Mechanisms of Neuroprotection by Presenilin1
Anastasios Georgakopoulos, Ph.D.
Mount Sinai School of Medicine
New York, New York
2011 Investigator-Initiated Research Grant
Presenilin1 (PS1) is a protein involved in the production of beta-amyloid, a protein fragment strongly implicated in the development of Alzheimer's disease. Mutations in PS1 are known to be a causative factor in some inherited forms of Alzheimer's disease, although the explanation for this link is not well understood.
In addition to its involvement in the production of beta-amyloid, PS1 is also crucial for the processing of numerous other proteins, allowing those proteins to perform their designated functions. One such protein is a receptor known as ephrinB2. Anastasios Georgakopoulos, Ph.D. and colleagues have shown that the ephrinB2 receptor protects nerve cells from certain types of toxicity and cell death. When PS1 is absent or dysfunctional, nerve cells lack this protection.
Dr. Georgakopoulos and colleagues have proposed to extend their studies of how PS1 protects nerve cells through processing of the ephrinB2 receptor, and how mutations in PS1 linked to Alzheimer's disease affect this process. The researches have also found evidence that mutations in PS1 cause an increase in another molecule known as microRNA-212. They have preliminary evidence that this molecule causes nerve cells to be more sensitive to toxic conditions. Dr. Georgakopoulos and colleagues plan to study ways to inhibit microRNA-212 in an attempt to identify treatments that reduce the death of nerve cells. These studies will explore pathways potentially linked to the decline of brain function in Alzheimer's disease, and they may help to identify drug candidates for preventing such decline.