Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function
Recent studies have highlighted that a novel class of neuroprotective peptide, known as cationic arginine-rich peptides (CARPs), have intrinsic neuroprotective properties and are particularly effective anti-excitotoxic agents. As such, the present study investigated the mechanisms underlying the ant...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/13/2977 |
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| author | Gabriella MacDougall Ryan S. Anderton Amy Trimble Frank L. Mastaglia Neville W. Knuckey Bruno P. Meloni |
| author_facet | Gabriella MacDougall Ryan S. Anderton Amy Trimble Frank L. Mastaglia Neville W. Knuckey Bruno P. Meloni |
| author_sort | Gabriella MacDougall |
| collection | DOAJ |
| description | Recent studies have highlighted that a novel class of neuroprotective peptide, known as cationic arginine-rich peptides (CARPs), have intrinsic neuroprotective properties and are particularly effective anti-excitotoxic agents. As such, the present study investigated the mechanisms underlying the anti-excitotoxic properties of CARPs, using poly-arginine-18 (R18; 18-mer of arginine) as a representative peptide. Cortical neuronal cultures subjected to glutamic acid excitotoxicity were used to assess the effects of R18 on ionotropic glutamate receptor (iGluR)-mediated intracellular calcium influx, and its ability to reduce neuronal injury from raised intracellular calcium levels after inhibition of endoplasmic reticulum calcium uptake by thapsigargin. The results indicate that R18 significantly reduces calcium influx by suppressing iGluR overactivation, and results in preservation of mitochondrial membrane potential (ΔΨm) and ATP production, and reduced ROS generation. R18 also protected cortical neurons against thapsigargin-induced neurotoxicity, which indicates that the peptide helps maintain neuronal survival when intracellular calcium levels are elevated. Taken together, these findings provide important insight into the mechanisms of action of R18, supporting its potential application as a neuroprotective therapeutic for acute and chronic neurological disorders. |
| first_indexed | 2024-03-10T18:48:59Z |
| format | Article |
| id | doaj.art-052373e68f1d49f6b407a510230b0137 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:48:59Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-052373e68f1d49f6b407a510230b01372023-11-20T05:14:55ZengMDPI AGMolecules1420-30492020-06-012513297710.3390/molecules25132977Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial FunctionGabriella MacDougall0Ryan S. Anderton1Amy Trimble2Frank L. Mastaglia3Neville W. Knuckey4Bruno P. Meloni5Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA 6009, AustraliaRecent studies have highlighted that a novel class of neuroprotective peptide, known as cationic arginine-rich peptides (CARPs), have intrinsic neuroprotective properties and are particularly effective anti-excitotoxic agents. As such, the present study investigated the mechanisms underlying the anti-excitotoxic properties of CARPs, using poly-arginine-18 (R18; 18-mer of arginine) as a representative peptide. Cortical neuronal cultures subjected to glutamic acid excitotoxicity were used to assess the effects of R18 on ionotropic glutamate receptor (iGluR)-mediated intracellular calcium influx, and its ability to reduce neuronal injury from raised intracellular calcium levels after inhibition of endoplasmic reticulum calcium uptake by thapsigargin. The results indicate that R18 significantly reduces calcium influx by suppressing iGluR overactivation, and results in preservation of mitochondrial membrane potential (ΔΨm) and ATP production, and reduced ROS generation. R18 also protected cortical neurons against thapsigargin-induced neurotoxicity, which indicates that the peptide helps maintain neuronal survival when intracellular calcium levels are elevated. Taken together, these findings provide important insight into the mechanisms of action of R18, supporting its potential application as a neuroprotective therapeutic for acute and chronic neurological disorders.https://www.mdpi.com/1420-3049/25/13/2977poly-arginine-18 (R18)cationic arginine-rich peptides (CARPs)neuroprotectionROSmitochondrial membrane potential (ΔΨm)ionotropic glutamate receptors |
| spellingShingle | Gabriella MacDougall Ryan S. Anderton Amy Trimble Frank L. Mastaglia Neville W. Knuckey Bruno P. Meloni Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function Molecules poly-arginine-18 (R18) cationic arginine-rich peptides (CARPs) neuroprotection ROS mitochondrial membrane potential (ΔΨm) ionotropic glutamate receptors |
| title | Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function |
| title_full | Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function |
| title_fullStr | Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function |
| title_full_unstemmed | Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function |
| title_short | Poly-arginine-18 (R18) Confers Neuroprotection through Glutamate Receptor Modulation, Intracellular Calcium Reduction, and Preservation of Mitochondrial Function |
| title_sort | poly arginine 18 r18 confers neuroprotection through glutamate receptor modulation intracellular calcium reduction and preservation of mitochondrial function |
| topic | poly-arginine-18 (R18) cationic arginine-rich peptides (CARPs) neuroprotection ROS mitochondrial membrane potential (ΔΨm) ionotropic glutamate receptors |
| url | https://www.mdpi.com/1420-3049/25/13/2977 |
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