Friday, May 5, 2023

Neurology/Neuroscience Research Seminar

12:00 PM to 1:00 PM

CME credit is available, click here

Attendance must be registered within 6 months of attendance to be awarded credit.

Recorded archives of live activities are considered enduring materials.

Viewing of a recorded session is for reference only, no CME credit can be claimed.

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“RNA-based regulation of TDP-43 nuclear localization”

Lindsey Hayes, M.D., Ph.D.

Associate Professor of Neurology

TDP-43 cytoplasmic mislocalization and loss of function is a hallmark of neurodegeneration in ALS and other TDP-43 proteinopathies and an important therapeutic target. In an effort to better understand potential upstream causes of TDP-43 mislocalization in disease, we investigated the mechanism and regulation of TDP-43 nuclear export, and found that TDP-43 exits the nucleus by passive diffusion. The normal predominantly nuclear localization of TDP-43 is maintained by binding to nuclear pre-mRNAs at GU-rich motifs. This model suggests that disregulation of RNA metabolism may be upstream of TDP-43 mislocalization in disease, and that RNA-based strategies may be useful to rescue TDP-43 nuclear localization and function. Candidate strategies in development will be discussed.