Alzheimer's disease (AD) is the most prevalent but still incurable neurodegenerative form of dementia. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. We herein report a novel fluoro-substituted cyanine, F-SLOH, which exhibits good A beta oligomer selectivity with a high binding affinity, attributed to the synergistic effect of strong pi-pi stacking and intermolecular CH...O and CH...F interactions. The selectivity towards the A beta oligomers in the brain was ascertained by in vitro labelling on tissue sections and in vivo labelling through the systemic administration of F-SLOH in 7 month APP/PS1 double transgenic (Tg) and APP/PS1/Tau triple Tg mouse models. F-SLOH also shows remarkably effective inhibition on Ab aggregation and highly desirable neuroprotective effects against A beta-induced toxicities, including the inhibition of ROS production and Ca2+ influx. Its excellent blood-brain barrier (BBB) penetrability and low bio-toxicity further support its tremendous potential as a novel theranostic agent for both early diagnosis and therapy of AD.
[1]Xiangtan Univ, Key Lab Green Organ Synth & Applicat Hunan Prov, Key Lab Environmentally Friendly Chem, Applicat Minist Educ,Coll Chem, Xiangtan 411105, Peoples R China.
[2]Shanghai Univ Med & Hlth Sci, Lab Neurodegenerat Dis & Mol Imaging, Shanghai 201318, Peoples R China.
[3]Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China.
[4]Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China.
[5]Liaocheng Univ, Sch Pharm, Liaocheng 252059, Peoples R China.
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