Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides
Spontaneous cleavage reactions normally occur in vivo on amino acid peptide backbones, leading to fragmentation products that can have different physiological roles and toxicity, particularly when the substrate of the hydrolytic processes are neuronal peptides and proteins highly related to neurodeg...
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MDPI AG
2025-01-01
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| author | Valentina Pirota Enrico Monzani Simone Dell’Acqua Chiara Bacchella |
| author_facet | Valentina Pirota Enrico Monzani Simone Dell’Acqua Chiara Bacchella |
| author_sort | Valentina Pirota |
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| description | Spontaneous cleavage reactions normally occur in vivo on amino acid peptide backbones, leading to fragmentation products that can have different physiological roles and toxicity, particularly when the substrate of the hydrolytic processes are neuronal peptides and proteins highly related to neurodegeneration. We report a hydrolytic study performed with the HPLC-MS technique at different temperatures (4 °C and 37 °C) on peptide fragments of different neuronal proteins (amyloid-β, tau, and α-synuclein) in physiological conditions in the presence of Cu<sup>2+</sup> and Zn<sup>2+</sup> ions, two metal ions found at millimolar concentrations in amyloid plaques. The coordination of these metal ions with these peptides significantly protects their backbones toward hydrolytic degradation, preserving the entire sequences over two weeks in solution, while the free peptides in the same buffer are fully fragmented after the same or even shorter incubation period. Our data show that peptide cleavage is not only ruled by the chemical sensitivity of amino acids, but the peptide conformation changes induced by metal coordination influence hydrolytic reactions. The enhanced stability of neuronal peptides provided by metal coordination can increase local levels of amyloidogenic species capable of seeding fibril growth, resulting in aberrant protein depositions and deficits in neuronal activity. |
| format | Article |
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| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Molecules |
| spelling | doaj-art-0e6a6bfd2417490cbc8ac30369fdad6d2025-01-24T13:43:47ZengMDPI AGMolecules1420-30492025-01-0130236310.3390/molecules30020363Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related PeptidesValentina Pirota0Enrico Monzani1Simone Dell’Acqua2Chiara Bacchella3Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, ItalyDipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, ItalyDipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, ItalyDipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, ItalySpontaneous cleavage reactions normally occur in vivo on amino acid peptide backbones, leading to fragmentation products that can have different physiological roles and toxicity, particularly when the substrate of the hydrolytic processes are neuronal peptides and proteins highly related to neurodegeneration. We report a hydrolytic study performed with the HPLC-MS technique at different temperatures (4 °C and 37 °C) on peptide fragments of different neuronal proteins (amyloid-β, tau, and α-synuclein) in physiological conditions in the presence of Cu<sup>2+</sup> and Zn<sup>2+</sup> ions, two metal ions found at millimolar concentrations in amyloid plaques. The coordination of these metal ions with these peptides significantly protects their backbones toward hydrolytic degradation, preserving the entire sequences over two weeks in solution, while the free peptides in the same buffer are fully fragmented after the same or even shorter incubation period. Our data show that peptide cleavage is not only ruled by the chemical sensitivity of amino acids, but the peptide conformation changes induced by metal coordination influence hydrolytic reactions. The enhanced stability of neuronal peptides provided by metal coordination can increase local levels of amyloidogenic species capable of seeding fibril growth, resulting in aberrant protein depositions and deficits in neuronal activity.https://www.mdpi.com/1420-3049/30/2/363peptide hydrolytic degradationmetal ion complexesLC-MS analysisneurodegenerative diseases |
| spellingShingle | Valentina Pirota Enrico Monzani Simone Dell’Acqua Chiara Bacchella Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides Molecules peptide hydrolytic degradation metal ion complexes LC-MS analysis neurodegenerative diseases |
| title | Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides |
| title_full | Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides |
| title_fullStr | Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides |
| title_full_unstemmed | Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides |
| title_short | Role of Copper and Zinc Ions in the Hydrolytic Degradation of Neurodegeneration-Related Peptides |
| title_sort | role of copper and zinc ions in the hydrolytic degradation of neurodegeneration related peptides |
| topic | peptide hydrolytic degradation metal ion complexes LC-MS analysis neurodegenerative diseases |
| url | https://www.mdpi.com/1420-3049/30/2/363 |
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