Monitoring Lysosomal Viscosity in Hyperglycemia in Association with Ca²⁺ Homeostasis and Alzheimer's Disease Using a...

A bright, photostable, and less-toxic fluorescent Zn-metal complex is reported to monitor lysosomal viscosity in hyperglycemia associated with Ca²⁺ homeostasis and in vivo Alzheimer's disease. A series of Zn-salen (Sl) complexes (Zn-Sl-X), where X = methoxy (-OCH₃), pyrrolidine (-Py), N,N-diethyl amine (-NEt₂), and N-methyl-N-propyl morpholine (-MPM), were synthesized. Among them, the synergistic effect of MPM in the Zn-Sl-MPM complex efficiently acts as both a viscosity sensor and the specific staining agent for lysosomes. The pronounced fluorescence response within lysosomes arises due to restricted intramolecular rotation (RIR) of the MPM unit in a viscous medium under hyperglycemic conditions. Our findings suggested that lysosomal viscosity is exclusively associated with Ca²⁺ imbalance in hyperglycemia and in Alzheimer's disease in vivo in Caenorhabditis elegans (C. elegans). Further, super-resolution radial fluctuation (SRRF) microscopy helped to observe the lysosomal swelling with an increased size in hyperglycemia.