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Recording γ-secretase activity in living mouse brains.

Steven S Hou | Yuya Ikegawa | Yeseo Kwon | Natalia Wieckiewicz | Mei C Q Houser | Brianna Lundin | Brian J Bacskai | Oksana Berezovska | Masato Maesako
eLife | 2024

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Förster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of γ-secretase activity on a cell-by-cell basis in live neurons in culture. Nevertheless, how γ-secretase activity is regulated in vivo remains unclear. Here, we employ the near-infrared (NIR) C99 720-670 biosensor and NIR confocal microscopy to quantitatively record γ-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that γ-secretase activity may influence the activity of γ-secretase in neighboring neurons, suggesting a potential 'cell non-autonomous' regulation of γ-secretase in mouse brains. Given that γ-secretase plays critical roles in important biological events and various diseases, our new assay in vivo would become a new platform that enables dissecting the essential roles of γ-secretase in normal health and diseases.

Pubmed ID: 39360803

Associated grants

  • Agency: NIA NIH HHS, United States
    Id: K01 AG072046
  • Agency: NIA NIH HHS, United States
    Id: R01 AG044486
  • Agency: NIA NIH HHS, United States
    Id: AG072046
  • Agency: NIA NIH HHS, United States
    Id: R01 AG079838
  • Agency: NIA NIH HHS, United States
    Id: AG015379
  • Agency: BrightFocus Foundation,
    Id: A2019056F
  • Agency: NIA NIH HHS, United States
    Id: P01 AG015379
  • Agency: NIA NIH HHS, United States
    Id: AG079838
  • Agency: NIA NIH HHS, United States
    Id: RF1 AG044486
  • Agency: NIA NIH HHS, United States
    Id: AG044486

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