Phenothiazine-based theranostic compounds for in vivo near-infared fluorescence imaging of β-amyloid plaques and inhibition of Aβ aggregation
Résumé
A global burden of Alzheimer's disease (AD) has been growing over last decades. Evidence indicates that β-amyloid (Aβ) production and senile plaque deposition in the brain is causative in the onset of AD pathogenesis. It appears much earlier than cognitive decline and plays a key role in initiating and developing AD neuropathology. As such, there is an intense passion with discovering theranostic agents which make a significant impact in diagnostic and therapy. Herein, we report an investigation of novel phenothiazine-based compounds as promising potential theranostic agents for AD. Remarkably, they have exhibited a high binding affinity toward Aβ aggregates, a good biostability and a strong increase in their fluorescence intensity with blue shift when interacting with Aβ aggregates. Furthermore, they have been simultaneously applied to perform NIR in vivo imaging of β-amyloid plaques in double transgenic AD mouse model, to prevent self-aggregation of Aβ monomer from forming toxic oligmers and to reduce Aβ-induced toxicity of human neuroblastoma cells (SH-SY5Y).
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