Bogyo and colleagues developed a new generation of fluorescent quenched activity-based probes that can be used to visualize the dynamics of active proteases in whole animals. These elegant probes combine the “quenching” feature, which offers the advantage of igniting only the active protease, with the near-infrared fluorescent conjugates to reduce background in in-vivo imaging.

Accumulating evidence supports the involvement of cysteine proteases in AD pathogenesis. For example, our recent study provides evidence that cathepsin B plays a role in amyloid-β degradation and clearance, suggesting that the deficiency and dysregulation of cysteine proteases may lead to Aβ accumulation. To fully understand the improper functions of cysteine proteases in AD, we need to be able to detect the activity of specific cysteine protease at the point of action and in real time. With a proper delivery method, the probes developed by Bogyo and colleagues may be well suited to do just that.

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