Ayala Lab Studies TDP-43 and ALS

Ribbon and surface representation of TDP-43 RRM1–2 fragment (amino acids 102–269) bound to a UG-rich RNA molecule (gray) based on an NMR structure of the complex (36). Thr-153 and Tyr-155 are highlighted in red.
Ribbon and surface representation of TDP-43 RRM1–2 fragment (amino acids 102–269) bound to a UG-rich RNA molecule (gray) based on an NMR structure of the complex (36). Thr-153 and Tyr-155 are highlighted in red.

Yuna Ayala, Ph.D., recently published a paper in the The Journal of Biological Chemistry detailing studies on TAR DNA-binding Protein 43 (TDP-43) and its role in neurodegenerative diseases, such as amytrophic lateral sclerosis (ALS).

TDP-43 regulates gene expression through RNA processing, and is essential for development and survival. It also forms intracellular aggregates in ALS and some other neurological diseases, resulting in loss of function of normal TDP-43. The researchers found that double phosphorylation of TDP-43 by MEK, a kinase in the MAPK/ERK signaling pathway that is activated by cellular heat shock response (HSR), did not aggregate and showed decreased splicing activity. These results uncovered a previously unknown mechanism of regulation for TDP-43, which could lead to new strategies to treat aggregation as well as new roles of TDP-43 in cellular metabolism.

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Department of Biochemistry and Molecular Biology
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