Nuclear Profilin‐1 for DNA Damage Repair Is Involved in Phagocytic Impairment of Senescent Microglia DOI
Chan Rim, Soyoung Sung,

Hui‐Ju Kim

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

ABSTRACT Accumulation of DNA damage is a hallmark cellular senescence and plays critical role in brain aging. Although the repair mechanisms are crucial senescence, they not well understood microglia. In this study, we found that profilin‐1 (PFN1), an actin‐binding protein, relocates from cytoplasm to nucleus response double‐strand breaks (DSBs) induced by doxorubicin. This nuclear PFN1 subsequently translocates back during recovery period. DSBs, detected enhanced expression genes associated with nonhomologous end joining (NHEJ), but homologous recombination (HR), along increased F‐actin accumulation. However, process compromised when either knocked down or its transport blocked. Notably, damage‐induced senescent microglia, localization formation phagocytic dysfunction. Both ex vivo aged microglia publicly available single‐cell RNA sequencing data mouse brains recapitulate vitro findings described above. Despite cytochalasin D treatment for actin depolymerization, return was facilitated due aggregation. We propose important addition, dysregulation nucleocytoplasmic balance alongside accumulation may contribute impairment brain.

Language: Английский

Nuclear Profilin‐1 for DNA Damage Repair Is Involved in Phagocytic Impairment of Senescent Microglia DOI
Chan Rim, Soyoung Sung,

Hui‐Ju Kim

et al.

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: May 3, 2025

ABSTRACT Accumulation of DNA damage is a hallmark cellular senescence and plays critical role in brain aging. Although the repair mechanisms are crucial senescence, they not well understood microglia. In this study, we found that profilin‐1 (PFN1), an actin‐binding protein, relocates from cytoplasm to nucleus response double‐strand breaks (DSBs) induced by doxorubicin. This nuclear PFN1 subsequently translocates back during recovery period. DSBs, detected enhanced expression genes associated with nonhomologous end joining (NHEJ), but homologous recombination (HR), along increased F‐actin accumulation. However, process compromised when either knocked down or its transport blocked. Notably, damage‐induced senescent microglia, localization formation phagocytic dysfunction. Both ex vivo aged microglia publicly available single‐cell RNA sequencing data mouse brains recapitulate vitro findings described above. Despite cytochalasin D treatment for actin depolymerization, return was facilitated due aggregation. We propose important addition, dysregulation nucleocytoplasmic balance alongside accumulation may contribute impairment brain.

Language: Английский

Citations

0