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2016 Grants - Lee, H
Pathological Role of PLK1 in Selective Neurodegeneration in Alzheimer’s Disease
Hyoung-gon Lee, Ph.D.
Case Western Reserve University
2016 Alzheimer’s Association Research Grant (AARG)
Can blocking the cell-cycle protein PLK1 help prevent nerve cell death during Alzheimer’s disease?
Nerve cells in the brain perform very specialized functions and form complex networks with other nerve cells. Unlike other cells in the body, most nerve cells do not divide – this helps in part to avoid disruptions in nerve cell networks. In cells that do divide, “cell cycle” is the term that describes the normal process they undergo to properly divide and replace damaged or aging cells. During Alzheimer’s disease, nerve cells sometimes attempt to abnormally re-enter the cell cycle. Re-entry into the cell cycle can unfortunately cause nerve cell death, or neurodegeneration. Understanding why nerve cells attempt to re-enter the cell cycle could help researchers develop new therapies to target this process and prevent nerve cells loss during Alzheimer’s disease.
Hyoung-gon Lee, Ph.D. and colleagues are studying how a protein called polo-like kinase 1 (PLK1), a known regulator of the cell cycle, may be contributing to neurodegeneration during Alzheimer’s disease. In initial studies, Dr. Lee found that the nerve cells most vulnerable to damage during Alzheimer’s disease had unusually high levels of PLK1. This suggests that PLK1 may be triggering nerve cell death. For their current studies, Dr. Lee and colleagues plan to block PLK1 protein in two types of Alzheimer’s-like mice. Molecules that inhibit PLK1 activity are widely available as they are also used to treat certain cancers. The researchers hope that by inhibiting PLK1, they can prevent neurodegeneration related to abnormal cell cycle re-entry in Alzheimer’s disease.
This research could shed new light on the molecular mechanisms that contribute to nerve cell loss during Alzheimer’s disease. Ultimately, this work could lead to a new therapeutic use for PLK1 inhibitors, and a possible new treatment option to slow or stop the progression of Alzheimer’s disease.