GFP-based red-emissive fluorescent probes for dual imaging of ß-amyloid plaques and mitochondrial viscosity.

Alzheimer's disease (AD), with incurable neurodegenerative damage, has attracted growing interest in exploration of better AD biomarkers in its early diagnosis. Among various biomarkers, amyloid-ß (Aß) aggregates and mitochondrial viscosity are closely related to AD and their dual imaging might provide a potential and feasible strategy. In this work, five GFP-based red-emissive fluorescent probes were rationally designed and synthesized for selective detection of ß-amyloid plaques and viscosity, among which C25e exhibited superior properties and could successfully image ß-amyloid plaques and mitochondrial viscosity with different fluorescence wavelength signals "turn-on" at around 624 and 640 nm, respectively. Moreover, the staining of brain sections from a transgenic AD mouse showed that probe C25e showed higher selectivity and signal-to-noise ratio towards Aß plaques than commercially-available Thio-S. In addition, the probe C25e was, for the first time, employed for monitoring amyloid-ß induced mitochondrial viscosity changes. Therefore, this GFP-based red-emissive fluorescent probe C25e could serve as a dual-functional tool for imaging ß-amyloid plaques and mitochondrial viscosity, which might provide a unique strategy for the early diagnosis of Alzheimer's disease.

Dual-Emission GFP Chromophore-Based Derivative for Imaging and Discriminating Aß Oligomers and Aggregates.

ß-Amyloid deposition is one of the main pathological features of Alzheimer's disease (AD). The development of fluorescent probes targeting specific ß-amyloid species has recently become an attractive strategy to achieve the early diagnosis of AD. In this work, a dual-channel fluorescent protein chromophore derivative C17 was rationally designed and synthesized for the detection and discrimination of Aß42 aggregates and oligomers. C17 exhibits a specific turn-on emission peak for Aß42 oligomers at ∼470 nm (peak A) and a peak at ∼600 nm (peak B) for both Aß42 oligomers and Aß42 aggregates. Taking advantage of the dual emission of the probe, the dynamic aggregation process of the Aß42 peptide was monitored in solution. Moreover, double staining of brain sections from transgenic AD mice revealed that peak A of C17 preferentially detected Aß42 oligomers, whereas peak B was more sensitive to Aß42 aggregates. The fact that probe C17 can be used for dissecting these two Aß42 species makes C17 a comprehensive tool for ß-amyloid aggregation studies in AD research.

Novel cationic meso-CF3 BODIPY-based AIE fluorescent rotors for imaging viscosity in mitochondria.

Two novel meso-CF3 BODIPY-based fluorescent rotors have been rationally prepared and found to sensitively respond to viscosity in living cells with a fluorescence "turn-on" effect, attributed to the special restricted rotation of meso-CF3 group in viscous environments. Interestingly, a monostyryl probe with one cationic group exhibits good mitochondrial localization and AIE property.