Merocyanine derivative for real-time imaging of amyloid-β and inhibition of self-aggregation and MAO-B activity

Area of Science:

• Neuroscience
• Biochemistry
• Medical Imaging

Background:

• Alzheimer's disease (AD) is a neurodegenerative disorder with unmet diagnostic and therapeutic needs.
• Amyloid-β (Aβ) aggregation and Monoamine Oxidase B (MAO-B) dysregulation are key factors in AD pathogenesis.
• Developing agents for simultaneous diagnosis and therapy of AD is a critical research goal.

Purpose of the Study:

• To synthesize and evaluate novel merocyanine derivatives as fluorescent probes for Aβ aggregates.
• To incorporate a MAO-B targeting pharmacophore for integrated diagnosis and therapy.
• To assess the theranostic potential of the developed probes in Alzheimer's disease models.

Main Methods:

• Synthesis of donor-π-acceptor (D-π-A) merocyanine derivatives.
• In vitro and in vivo imaging of Aβ aggregates using fluorescent probes.
• Assessment of MAO-B inhibition, Aβ aggregation inhibition, and antioxidant activity.
• Evaluation of probe cytotoxicity and selectivity in cellular and animal models.

Main Results:

• The probe LA4-1 demonstrated high-sensitivity imaging of Aβ aggregates in cellular and AD mouse models.
• LA4-1 exhibited significant inhibition of Aβ aggregation (97%) and MAO-B activity (89%).
• The probe showed good MAO-B selectivity, low cytotoxicity, and antioxidant capabilities.

Conclusions:

• LA4-1 functions as a potent theranostic agent for Alzheimer's disease.
• The probe offers superior Aβ imaging and multimodal therapeutic actions.
• This research provides a foundation for developing advanced Aβ-targeted theranostic agents for AD.