N-Methyl Mesoporphyrin IX as an Effective Probe for Monitoring Alzheimer's Disease β-Amyloid Aggregation in Living Cells.

Abstract

Formation of amyloid fibrils by amyloid-β peptide (Aβ) is an important step in Alzheimer's disease (AD) progression. Screening and designing of new molecules which can monitor the amyloidosis process especially in cells are diagnostically and therapeutically important. Utilizing Thioflavin T (ThT), the commonly used amyloid dye, is the most standardized way to monitor amyloid. However, with the green fluorescence emission and small Stokes shift, the fluorescence of ThT can overlap with that arising from other intrinsic fluorescent components in the cells, making it not suitable for detection of protein aggregates in vivo. Therefore, it is urgent for developing amyloid probes with large Stokes shifts and red-shifted fluorescence emission to detect Aβ aggregates in cells. In this report, we found that N-methyl mesoporphyrin IX (NMM), a widely used G-quadruplex DNA specific fluorescent binder, can be an efficient probe for monitoring Aβ fibrillation in living cells. NMM is nonfluorescent in aqueous solution or monomeric Aβ environments. However, through stacking with the Aβ assemblies, NMM emits strong fluorescence. Furthermore, the large Stokes shift and stable photoluminescence make it an ideal probe for detecting Aβ aggregates in highly fluorescent environments and cell culture. Our results provide a new sight to design and screen new reagents for monitoring the diseases associated with protein conformational disorders.