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Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43 by Sean S. Keating; Adekunle T. Bademosi; Rebecca San Gil; Adam K. Walker is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43 about?

Aggregation of the RNA-binding protein, TDP-43, is the unifying hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43-related neurodegeneration involves multiple changes to normal physiological TDP-43, which undergoes nuclear depletion, cytoplasmic mislocalisation, post-translational modification, and aberrant liquid–liquid phase separation, preceding inclusion formation. Along with toxic cytoplasmic aggregation, concurrent depletion and dysfunction of normal nuclear TDP-43 in cells with TDP-43 pathology is likely a key potentiator of neurodegeneration, but is not well understood. To define processes driving TDP-43 dysfunction, we used CRISPR/Cas9-mediated fluorescent tagging to investigate how disease-associated stressors and pathological TDP-43 alter abundance, localisation, self-assembly, aggregation, solubility, and mobility dynamics of normal nuclear TDP-43 over time in live cells. Oxidative stress stimulated liquid–liquid phase separation of endogenous TDP-43 into droplet-like puncta, or spherical shell-like anisosomes. Further, nuclear RNA-binding-ablated or acetylation-mimicking TDP-43 readily sequestered and depleted free normal nuclear TDP-43 into

Who reads Aggregation-prone TDP-43 sequesters and drives pathological transitions of free nuclear TDP-43?

Author

Sean S. Keating; Adekunle T. Bademosi; Rebecca San Gil; Adam K. Walker

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)