Beta Amyloid-Induced Synaptic Plasticity Imbalance and Neurogranin
Principal Investigator
Project Goals
While the application of amyloid beta (a precursor of AD) decreases neurogranin levels and suppresses synaptic transmission, increasing neurogranin in hippocampal neurons was able to reverse the beta amyloid-induced depression in synaptic transmission. We are proposing to understand the mechanism by which neurogranin is capable of such reversal of synaptic function and to explore the possibility that neurogranin may be reversing the synaptic plasticity imbalance. Success of this proposal can open the door for new therapeutic intervention for AD.
Project Summary
Previous studies have found that the Alzheimer's disease beta‐amyloid protein negatively influences brain cells (neurons) and results in a communication breakdown by causing a loss of “plasticity” at the synapses (the place where neurons meet), leading to learning and memory loss. In a previous study, Dr. Nashaat Gerges and colleagues have shown that increasing neurogranin enhances the ability of the synapses to communicate. In this project, they will explore the possibility that neurogranin may reverse the negative effect of beta amyloid on synaptic plasticity. They will use a special technique that grows neurons in a dish, giving easy access for treatments and analysis of results. If successful, this could lead to future therapies for individuals with Alzheimer's disease.
Progress Updates
Dr. Gerges’ team has made significant progress toward understanding the mechanism by which neurogranin protein may be playing a role in reversing the negative effects on nerve cells that are caused by toxic beta-amyloid. As a major aim of this proposal, the team first tested the effect of beta-amyloid on a type of synaptic plasticity (the ability of the connections between nerve cells to change their strength) that is involved with learning and memory. Then, they assessed how neurogranin is involved in these changes, both by looking at the electrical signals sent between nerve cells and at the changes in expression of other cell proteins. The team needs to decide whether neurogranin is a candidate for a future Alzheimer’s disease therapy by determining if it can preserve the number of physical connections between nerve cells, thus helping to preserve memory.
First published on: July 06, 2011
Last modified on: December 22, 2024