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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. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures. Pretreatment with NB-02 prevented pathological calcium elevations in neurons and astrocytes after application of toxic soluble amyloid-β (Aβ) oligomers. NB-02 also prevented cell death associated with the addition of soluble Aβ oligomers suggesting NB-02 is effective at protecting both neurons and astrocytes from Aβ-mediated damage. [ABSTRACT FROM AUTHOR]