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A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
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Metal-Complexes Bearing Releasable CO Differently Modulate Amyloid Aggregation
Sara La Manna1, Valentina Roviello2, Fabiana Napolitano3
1Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
Inorganic Chemistry
|June 20, 2023
Summary
Three metal-based carbon monoxide-releasing molecules (CORMs) were tested for their impact on amyloid aggregation. Two CORMs promoted aggregation, while one inhibited it, suggesting potential for developing antiamyloidogenic agents.
Area of Science:
- Biochemistry
- Materials Science
- Medicinal Chemistry
Background:
- Neurodegenerative diseases are linked to uncontrolled protein aggregation, specifically amyloid formation.
- Modulating protein self-recognition is a key strategy for developing treatments.
Purpose of the Study:
- To investigate the effects of three novel metal-based carbon monoxide-releasing molecules (CORMs) on the aggregation of the amyloidogenic peptide fragment NPM1264-277.
- To explore the potential of these CORMs as antiamyloidogenic agents.
Main Methods:
- Synthesis and characterization of three metal complexes: Cym-Ade, Cym-Cipro, and Re-Flavo.
- Thioflavin T (ThT) assay, UV-vis absorption, fluorescence spectroscopy, scanning electron microscopy (SEM), and electrospray ionization mass spectrometry (ESI-MS) were employed.
- Analysis of peptide aggregation kinetics and fiber morphology.
Main Results:
- Cym-Ade and Cym-Cipro acted as aggregating agents, promoting the formation of longer and stiffer/thicker amyloid fibers.
- Irradiation of Cym-Ade accelerated fiber formation, yielding more flexible and thicker fibers.
- Re-Flavo demonstrated anti-aggregating properties, inhibiting NPM1264-277 self-assembly.
- The study revealed distinct aggregation modulation effects based on the CORM's structure.
Conclusions:
- Metal-based CORMs exhibit diverse effects on amyloid fiber formation, acting as either aggregators or inhibitors.
- The choice of ligands significantly influences the biological activity of CORMs.
- These findings highlight the potential for designing metal-based compounds as therapeutic agents against amyloid-related pathologies.
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