Recording γ-secretase activity in living mouse brains

γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Forster 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, h...

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Published inbioRxiv
Main Authors Hou, Steven S, Ikegawa, Yuya, Kwon, Yeseo, Wieckiewicz, Natalia, Houser, Mei C Q, Lundin, Brianna, Bacskai, Brian J, Berezovska, Oksana, Maesako, Masato
Format Journal Article
LanguageEnglish
Published United States 14.07.2024
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Summary:γ-Secretase plays a pivotal role in the central nervous system. Our recent development of genetically encoded Forster 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.
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ISSN:2692-8205
2692-8205
DOI:10.1101/2024.01.31.578105