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2020 Zenith Fellows Award Program (ZEN)

The Role of Parthanatos in Alzheimer's Disease

Does a protein known to play a role in nerve cell death in Parkinson’s disease play a similar role in Alzheimer’s?

Ted Dawson, M.D., Ph.D.
John Hopkins University School of Medicine
Baltimore, MD - United States


Activation of a protein called poly ADP-ribose polymerase (PARP-1) can cause nerve cell death during brain diseases, such as Parkinson’s. This type of cell death is called “parthanatos.” It is distinct from other kinds of cell death due to the proteins involved, including PARP-1 as well as another protein called macrophage migration inhibitor factor (MIF). Excessive activity of PARP-1 ultimately activates MIF; MIF is a protein that regulates specific aspects of the immune system. Past studies show that there is interplay between PARP-1 and MIF that contributes to cell death, but their role in Alzheimer’s has not yet been explored.

Research Plan

Dr. Ted Dawson and colleagues will explore PARP-1 and MIF activity using genetically-engineered Alzheimer’s-like mouse models. They will genetically engineer models to lack MIF. The researchers will determine if loss of MIF activity impacts brain changes in the mice, such as tau tangles and beta-amyloid plaques, both hallmarks of Alzheimer’s that can contribute to nerve cell death. Dr. Dawson believes that interfering with MIF—the last step in the parthanatos cell death process—may help prevent nerve cell death in the mice.


This study will be the first to rigorously investigate parthanatos in the context of Alzheimer’s disease. If loss of MIF activity helps prevent nerve cell death in the mice, it could potentially provide a completely new therapeutic avenue to influence the Alzheimer’s course. The findings could set the stage for testing MIF inhibitors in other Alzheimer’s models, and may ultimately help delay or prevent nerve cell death across several neurodegenerative diseases.

Made possible through the generous funding from the Zenith Society, benefiting the Alzheimer’s Association.

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