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Research Grants - 2012


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Research Grants 2012


To view an abstract, select an author from the vertical list on the left.

2012 Grants - Guo

CypD and Abeta-Impaired Axonal Mitochondrial Motility and Docking

Lan Guo, Ph.D.
University of Kansas Center for Research, Inc.
Lawrence, Kansas

2012 New Investigator Research Grant

Mitochondria are cellular components that normally provide energy and nutrients to the cell. During Alzheimer's disease, however, mitochondria in the brain become dysfunctional. Many lose their ability to move around in axons—the arm-like extensions of neurons that send out and receive chemical messages. This loss of movement damages the tiny, channel-like synapses through which axonal messages are sent. Recent evidence indicates that beta-amyloid, a protein fragment implicated in Alzheimer's disease, helps initiate the changes that lead to mitochondrial dysfunction. Yet the exact mechanisms by which this process occurs are unclear.

Lan Guo, Ph.D., and colleagues have been examining whether the enzyme cyclophilin D (cypD) may play a role in amyloid-induced mitochondrial damage. CypD is likely involved in "programmed cell death," a kind of self-destruct mechanism that eliminates faulty cells. But in Alzheimer's disease, cyclophilin levels may increase and cause unwanted damage to healthy cells. CypD interacts with the mitochondrial membrane, and it can promote the formation of membrane pores. Too much cypD activity may severely weaken the mitochondria, making them more vulnerable to dysfunction in Alzheimer's. This role of cypD has been confirmed in Dr. Guo's preliminary studies. When the researchers genetically depleted cycD from laboratory cells, they were able to moderate amyloid-induced mobility problems in the cell's mitochondria.

For their current project, Dr. Guo and colleagues will use their genetically modified cells to identify the mechanisms that explain how cypD and beta-amyloid hinder mitochondrial movement and synaptic function. The results of this work could lead to therapies that improve cognition by targeting cyclophilin D.