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2007 Grant - Conant
MMPs and Synaptic Injury in Alzheimer's Disease
Katherine Conant, M.D.
Johns Hopkins University
2007 Investigator-Initiated Research Grant
Synapses are tiny gaps that facilitate communication between neurons. Each of the billions of neurons in the brain can have thousands of synapses. Researchers now know that damage to these synapses is one of the first manifestations of Alzheimer's disease, coming well before the degeneration of complete neurons. Because it occurs so early in the disease, knowing what causes synaptic damage could help researchers better understand the fundamental pathology that drives Alzheimer's disease progression.
Katherine Conant and colleagues will investigate the role of matrix metalloproteinases, or MMPs, in synaptic damage. MMPs are a family of enzymes that digest other proteins. Though they can target proteins found in synapses, whether MMPs truly play a crucial role in regulating synapses is unclear. However, some of these enzymes are elevated in the Alzheimer brain, and they are released by immune cells in the brain that are activated during the disease. Furthermore, Conant and colleagues have preliminary evidence that MMPs can destroy synaptic receptors, which are "docking sites" for the chemical messengers that neurons use to communicate with each other.
The researchers plan to investigate the role of MMPs in synaptic structure and function. They will test whether inhibiting MMPs may help prevent Alzheimer-like disease seen in mice genetically engineered to mimic Alzheimer pathology. They believe that their work will help determine whether MMP inhibitors should be considered for use in clinical trials.