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2015 Grants - Llorens-Martín
GSK-3ß and Adult Neurogenesis: Therapeutic Potential for Alzheimer's Disease
María Llorens-Martín, Ph.D.
Center for Networked Biomedical Research on Neurodegenerative Diseases
2015 New Investigator Research Grant
Does GSK-3 beta protein contribute to the development of Alzheimer’s disease by preventing the generation of new nerve cells in the brain?
Recent studies have shown that certain brain regions produce new nerve cells throughout life in a process called neurogenesis. This constant regeneration likely helps protect the brain from neurodegenerative diseases such as Alzheimer’s, which involve the progressive loss of nerve cells. One brain region, the hippocampus, experiences more nerve cell regeneration than other regions. The hippocampus is vital for learning and memory and is affected early in Alzheimer’s disease. Recent research has shown that a protein called glycogen synthase kinase-3 beta (GSK-3 beta) becomes abnormally activated in Alzheimer’s disease. Such activation may inhibit the development and survival of new nerve cells in the hippocampus and other parts of the brain. However, scientists are unsure exactly how GSK-3 beta exerts its toxicity.
In initial studies with mice, María Llorens-Martín, Ph.D., and colleagues have found abnormal GSK-3 beta activity can damage hippocampal nerve cells in several ways. For example, it can promote inflammation in the brain that leads to nerve cell degeneration and death. However, GSK-3 beta may also affect nerve cell health more directly, in ways that do not involve brain inflammation.
For this grant, Dr. Llorens-Martín and colleagues plan to identify ways that GSK-3 beta directly promotes damage in the hippocampus. First, they will develop a novel mouse model that has high levels of GSK-3 beta but does not develop brain inflammation. This will allow them to study the effects of GSK-3 beta independently from brain inflammation. The team will then assess how GSK-3 beta activity affects the production of new hippocampal nerve cells and brain function in these mice.
The results of this study may shed new light on the involvement of GSK-3 beta in the earliest stages of Alzheimer’s disease. Additionally, these studies could help lead to the future development of nerve cell regeneration therapies for preventing or slowing Alzheimer’s disease progression.