YOPRO-1: A Cyanine-Based Molecular Rotor Probe for Amyloid Fibril Detection.

Area of Science:

• Biochemistry
• Spectroscopy
• Neuroscience

Background:

• Amyloidosis is prevalent in neurodegenerative diseases, necessitating improved early detection methods.
• Traditional amyloid detection tools lack sensitivity, specificity, and struggle with complex biological samples.
• Existing probes like Thioflavin-T (ThT) have limitations, including poor blood-brain barrier penetration and low sensitivity to oligomers.

Purpose of the Study:

• To evaluate YOPRO-1 as a sensitive and selective fluorescent probe for amyloid fibril detection.
• To demonstrate YOPRO-1's efficacy in complex biological matrices, overcoming limitations of previous probes.
• To establish YOPRO-1 as a viable tool for early diagnosis of amyloid-related diseases.

Main Methods:

• Steady-state emission spectroscopy
• Ground-state absorption spectroscopy
• Time-resolved fluorescence spectroscopy
• Molecular docking simulations

Main Results:

• YOPRO-1 exhibits a turn-on fluorescence response specific to amyloid fibrils.
• A significant 245-fold fluorescence enhancement was observed upon YOPRO-1 binding to insulin fibrils.
• YOPRO-1 demonstrated effective amyloid detection in high-percentage human serum, a challenging matrix.
• Molecular docking confirmed YOPRO-1's high affinity and selectivity for amyloid structures.

Conclusions:

• YOPRO-1 is a highly sensitive and selective fluorescent probe for amyloid fibrils.
• Its ability to function in complex biological matrices represents a significant advancement in amyloid detection.
• YOPRO-1 holds promise for the early diagnosis and understanding of amyloid-related neurodegenerative diseases.