Dr. Suzanne Zukin, at Albert Einstein College of Medicine, is expert on signaling pathways in the brain and synaptic plasticity. With this 2017 grant of $90,000 from FRAXA Research Foundation, she and her team are exploring autophagy, which is how cells clean house, in Fragile X.
FRAXA Research Foundation has awarded Dr. Zukin’s team a total of $345,000 in grants.
Autophagy is a natural process of programmed degradation and recycling of components of cells. It’s the cells’ system of cleaning house. In Fragile X syndrome, autophagy seems to be underactive.
Dr. Zukin and colleagues have previously studied a particular “master regulator” protein, the mammalian target of rapamycin complex 1 (mTORC1), and found that it is overactivated in the hippocampus of Fragile X mice. Too much mTORC1 leads to too little of the cleanup system (‘autophagy’) and therefore too much of many other proteins.
The Zukin team will examine whether impaired autophagy causes impaired learning in Fragile X mice. They will also investigate whether it can explain the differences seen in the structure of spine-like protrusions on dendrites (connections between neurons), which in Fragile X mimic an immature morphology (shape). Then they will look for novel therapeutic strategies that target the autophagy pathway to rescue autophagy and learning in Fragile X mice.