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How might a protein related to calcium molecules help preserve nerve cell communication during Alzheimer’s disease?
Peng Zhang, Ph.D.
University of Virginia
Charlottesville, VA - United States
Background
Nerve cells communicate with each other through specialized cell structures called synapses. When synapses are damaged, nerve cells are limited by how effectively they can communicate with one another. Poor nerve cell communication contributes to decline of memory and cognition. Recent studies have found that when synapses are damaged there are early declines in synapse function, called “synaptic depression,” and this change often precedes cognitive decline associated with Alzheimer’s disease.
While molecular mechanisms that underlie synaptic depression are not fully understood, prior work by Dr. Peng Zhang suggests high levels of a protein called Cdk5 (cyclin-dependent kinase 5) can harm synapses. Based on these findings, Dr. Zhang believes that blocking the activity of Cdk5 could serve as a promising strategy to preserve synapses during Alzheimer’s disease.
Research Plan
Dr. Zhang will study how a naturally occurring protein called Cav3.2—that transports calcium molecules inside nerve cells—could be used to lower the Cdk5 levels associated with the biological changes in Alzheimer’s disease. Using nerve cells growing in laboratory dishes, Dr. Zhang and his team will examine how activation of Cav3.2 influences other proteins inside these nerve cells and whether increasing Cav3.2 activity ultimately lowers Cdk5 levels.
In a second aim of the study, Dr. Zhang will test the role of Cav3.2 in genetically engineered Alzheimer’s-like mice. Dr. Zhang’s team will investigate whether Cdk5 levels are higher in these Alzheimer’s-like mice compared to mice that do not have the Alzheimer’s-like brain changes, and whether activating Cav3.2 can help lower them. Finally, Dr. Zhang will determine if increasing Cav3.2 activity can help avoid loss of synapses and prevent cognitive dysfunction in these mouse models.
Impact
If successful, this study could pave the way for a new therapeutic target for preserving nerve cell communication during Alzheimer’s disease.
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