Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase
Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/8/3947 |
| _version_ | 1797538094327529472 |
|---|---|
| author | Ida Cariati Roberto Bonanni Mario Marini Anna Maria Rinaldi Beatrice Zarrilli Virginia Tancredi Claudio Frank Giovanna D’Arcangelo Marco Diociaiuti |
| author_facet | Ida Cariati Roberto Bonanni Mario Marini Anna Maria Rinaldi Beatrice Zarrilli Virginia Tancredi Claudio Frank Giovanna D’Arcangelo Marco Diociaiuti |
| author_sort | Ida Cariati |
| collection | DOAJ |
| description | Salmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. In particular, it has been proposed that an electrostatic interaction may be responsible for the initial contact between prefibrillar oligomers and GM1 contained in lipid rafts. Based on this evidence, the aim of our work was to investigate whether the neurotoxic action induced by calcitonin prefibrillar oligomers could be counteracted by treatment with neuraminidase, an enzyme that removes sialic acid residues from gangliosides. Therefore, we studied cell viability in HT22 cell lines and evaluated the effects on synaptic transmission and long-term potentiation by in vitro extracellular recordings in mouse hippocampal slices. Our results showed that treatment with neuraminidase alters the surface charges of lipid rafts, preventing interaction between the calcitonin prefibrillar oligomers and GM1, and suggesting that the enzyme, depending on the concentration used, may have a partial or total protective action in terms of cell survival and modulation of synaptic transmission. |
| first_indexed | 2024-03-10T12:25:37Z |
| format | Article |
| id | doaj.art-f37c64c58a98436fa4d5ff2bf6b56dd4 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:25:37Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f37c64c58a98436fa4d5ff2bf6b56dd42023-11-21T15:06:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228394710.3390/ijms22083947Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of NeuraminidaseIda Cariati0Roberto Bonanni1Mario Marini2Anna Maria Rinaldi3Beatrice Zarrilli4Virginia Tancredi5Claudio Frank6Giovanna D’Arcangelo7Marco Diociaiuti8Medical-Surgical Biotechnologies and Translational Medicine (Phd), Department of Clinical Sciences and Translational Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyUniCamillus-Saint Camillus International University of Health Sciences, Via di Sant’Alessandro 8, 00131 Rome, ItalyDepartment of Systems Medicine, “Tor Vergata” University of Rome, Via Montpellier 1, 00133 Rome, ItalyCentro Nazionale Malattie Rare, Istituto Superiore di Sanità, 00161 Rome, ItalySalmon calcitonin is a good model for studying amyloid behavior and neurotoxicity. Its slow aggregation rate allows the purification of low molecular weight prefibrillar oligomers, which are the most toxic species. It has been proposed that these species may cause amyloid pore formation in neuronal membranes through contact with negatively charged sialic acid residues of the ganglioside GM1. In particular, it has been proposed that an electrostatic interaction may be responsible for the initial contact between prefibrillar oligomers and GM1 contained in lipid rafts. Based on this evidence, the aim of our work was to investigate whether the neurotoxic action induced by calcitonin prefibrillar oligomers could be counteracted by treatment with neuraminidase, an enzyme that removes sialic acid residues from gangliosides. Therefore, we studied cell viability in HT22 cell lines and evaluated the effects on synaptic transmission and long-term potentiation by in vitro extracellular recordings in mouse hippocampal slices. Our results showed that treatment with neuraminidase alters the surface charges of lipid rafts, preventing interaction between the calcitonin prefibrillar oligomers and GM1, and suggesting that the enzyme, depending on the concentration used, may have a partial or total protective action in terms of cell survival and modulation of synaptic transmission.https://www.mdpi.com/1422-0067/22/8/3947amyloid neurotoxicitysalmon calcitoninsoluble prefibrillar oligomerslipid raftsGM1neuraminidase |
| spellingShingle | Ida Cariati Roberto Bonanni Mario Marini Anna Maria Rinaldi Beatrice Zarrilli Virginia Tancredi Claudio Frank Giovanna D’Arcangelo Marco Diociaiuti Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase International Journal of Molecular Sciences amyloid neurotoxicity salmon calcitonin soluble prefibrillar oligomers lipid rafts GM1 neuraminidase |
| title | Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase |
| title_full | Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase |
| title_fullStr | Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase |
| title_full_unstemmed | Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase |
| title_short | Role of Electrostatic Interactions in Calcitonin Prefibrillar Oligomer-Induced Amyloid Neurotoxicity and Protective Effect of Neuraminidase |
| title_sort | role of electrostatic interactions in calcitonin prefibrillar oligomer induced amyloid neurotoxicity and protective effect of neuraminidase |
| topic | amyloid neurotoxicity salmon calcitonin soluble prefibrillar oligomers lipid rafts GM1 neuraminidase |
| url | https://www.mdpi.com/1422-0067/22/8/3947 |
| work_keys_str_mv | AT idacariati roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT robertobonanni roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT mariomarini roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT annamariarinaldi roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT beatricezarrilli roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT virginiatancredi roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT claudiofrank roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT giovannadarcangelo roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase AT marcodiociaiuti roleofelectrostaticinteractionsincalcitoninprefibrillaroligomerinducedamyloidneurotoxicityandprotectiveeffectofneuraminidase |