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Jan 15

Research Bit: TDP-43 proteinopathy alters translation and neuronal metabolism – insights from fly models of ALS/FTD

Research Bits
The Packard Center welcomed Daniela Zarnescu, PhD from the University of Arizona to a recent Investigator's meeting.

Meeting Date: 15 January 2021

Presenter: Daniela Zarnescu, PhD

Talk Title: TDP-43 proteinopathy alters translation and neuronal metabolism – insights from fly models of ALS/FTD


What was the question being asked?

How is protein production different in cells with mutated TDP-43, and how can observations from fruit flies be translated into knowledge about the human disease?

Why is this important for ALS research?

Several labs have demonstrated that mutations in TDP-43 (one of the causes of inherited ALS) lead to alterations in the production of certain proteins in motor neurons. By studying which proteins are produced differently in neurons affected by ALS, we can make headway in two areas of research: 1) identifying genes that are negatively affected by the disease and 2) identifying ways that the affected neurons are responding to survive.

What was the take-home message?

Using a fruit fly model to study ALS, Dr. Zarnescu’s lab identified DLP as a gene with lower production in diseased compared to healthy neurons. Additionally, they determined that restoring DLP to its normal amount leads to a significantly healthier fly. When following-up their investigation in postmortem human tissue, they determined that the human homolog of DLP is abnormally accumulated in motor neurons, indicating that it may not be functioning correctly.

How do you think the results of this study might impact future approaches to the treatment of ALS?

As the disease progresses, motor neurons don’t just accept their degradation as inevitable. They put up a strong fight, upregulating pro-survival genes to compensate for the issues that arise from ALS. Dr. Zarnescu’s work paves the way for the development of therapies that can boost the effect of the neuron’s natural response to disease.

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