A Dual-Targeted Fluorescent Probe with a Semicurcumin Structure for Imaging β-Amyloid and α-Synuclein Aggregates

Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most prevalent neurodegenerative disorders, both characterized by abnormal protein folding. Amyloid-β (Aβ) and α-synuclein (α-syn) are often associated with these diseases, which might occur simultaneously in later stages. In this study, we developed a dual-target fluorescent probe, <b>DiFboron-6</b>, designed to specifically target Aβ and α-syn aggregates. <b>DiFboron-6</b> exhibited excellent fluorescence properties, with 59-fold and 49-fold increases in fluorescence intensity upon binding to Aβ and α-syn aggregates, respectively. The probe demonstrated strong binding affinity to both proteins, with dissociation constants of <i>K</i>d_Aβ = 12.4 nM and <i>K</i>d_α-syn = 174 nM. Mouse brain slice staining and <i>in vitro</i> experiments further confirmed that <b>DiFboron-6</b> could clearly label both protein plaques and effectively cross the blood-brain barrier (BBB). <b>DiFboron-6</b> has been shown to effectively detect both Aβ and α-syn aggregates, thereby serving as a dual-target detection tool. Its unique structure offers a promising foundation for the development of future dual-target probes.