Liam Chen, MD, PhD & Philip Wong, PhD
Johns Hopkins School of Medicine
Targeting TDP-43 repression of nonconserved cryptic exons in ALS-FTD
How TDP-43, a protein associated with a vast majority of ALS cases, causes malfunction of nerve cells remains a mystery. Depletion of this protein is thought to be responsible for killing nerve cells. We use mouse and fruit fly models that lack this TDP-43 protein to induce malfunction and death of nerve cells to help us identify drug targets for therapy. We now identify a target called Atg7, a critical protein needed to breakdown unnecessary or dysfunctional components in nerve cells. To validate this target, we propose to use a series of tests in mouse and fruit fly models. Specifically, we will test whether spermidine, a natural chemical compound produced in our body that stimulates production of this Atg7 protein, could provide benefit in our mouse and fruit fly models. Positive test outcomes from our proposal will allow us to validate this factor as a therapeutic target and hold promise for development of treatment strategies for ALS.
Note: This project is made possible through a collaboration with the Winokur Family Research Initiative and the ALS Association
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Gladstone Institutes, UCSF
Two recently discovered genes that have been associated with both familial and sporadic forms of ALS encode the related proteins TDP43 and FUS cause neuron death in ALS.
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