Aromaticity-driven laser photo-responses and binding efficiency in IAF-conjugated natural products for neurodegenerative disease targets

Alzheimer’s disease (AD) remains devastating neurodegenerative disorder with enormous societal and clinical impact, largely due to the challenge of detecting pathogenies changes early and the absence of effective disease-modifying treatments. Central to AD pathogenic is the dysregulated proteolytic processing of amyloid precursor protein (APP), primarily mediated by β-site APP cleaving enzyme (BACE1) which initiates the accumulation of amyloid-β (Αβ) peptides. The enzymes α-secretase (ADAM10) and the Aβ-degrading neprilysin are widely recognized as critical intervention points. Yet, there is a pressing need for probes that can both sensitively detect and modulate these targets in complex biological settings. 1 , 2 Current imaging and therapeutic agents often lack both the optical responsiveness and biochemical selectivity needed for early AD intervention. Integrating optical sensing with target-specific binding, supported by in silico docking and structure-based screening, now offer rational path toward precision for theranostic molecular probe. 3