A Renal Clearable Probe for In Vivo Monoamine Oxidase (MAO) Detection

Area of Science:

• Biomedical Engineering
• Biochemistry
• Medical Imaging

Background:

• Hyperactivation of monoamine oxidase (MAO) enzymes contributes to neurotoxic compound production, linked to neurodegenerative and age-related diseases.
• Current methods for MAO detection are often invasive, limiting in vivo monitoring.
• Non-invasive tools are needed to track MAO overexpression and its pathological implications.

Purpose of the Study:

• To develop a novel, renal-clearable fluorogenic probe for non-invasive in vivo detection of MAO activity.
• To establish a simple method for quantifying MAO overexpression by measuring urine fluorescence.
• To validate the probe's utility in cell models and aged animal studies.

Main Methods:

• Design and synthesis of a cyanine-7 (Cy7) based fluorogenic probe (Cy7-MAO) with sulfonic acid groups for renal clearance and a propylamino MAO substrate.
• In vitro validation using HepG2 liver cells with elevated MAO levels.
• In vivo testing in young and aged mice to assess MAO activity via urine fluorescence measurement.

Main Results:

• The Cy7-MAO probe successfully detected MAO activity in vitro.
• Administration of Cy7-MAO led to MAO-mediated hydrolysis, releasing a fluorescent Cy7 signal excreted in urine.
• Aged mice exhibited significantly higher urine fluorescence compared to young mice, indicating elevated MAO activity.

Conclusions:

• Cy7-MAO serves as an effective tool for the longitudinal, non-invasive assessment of MAO activity in vivo.
• This probe offers a novel approach for studying MAO-related pathologies and aging.
• Urine fluorescence measurement provides a simple and accessible method for MAO activity monitoring.