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

Marcia Domínguez1,2, David Azorín-Soriano1,3, Araceli Lérida-Viso1,2,3,4

  • 1Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Universitat Politècnica de València, Universitat de València, Valencia, Spain.

Insights

A new urine-detectable probe, Cy7-MAO, allows non-invasive monitoring of monoamine oxidase (MAO) enzyme activity in vivo. This breakthrough aids in studying MAO-related diseases and aging processes.

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.

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