Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease
Alzheimer’s disease (AD) is the most prevalent form of dementia and soluble amyloid β (Aβ) oligomers are thought to play a critical role in AD pathogenesis. Cellular prion protein (PrP<sup>C</sup>) is a high-affinity receptor for Aβ oligomers and mediates some of their toxic effects. The...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7273 |
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| author | Elham Rezvani Boroujeni Seyed Masoud Hosseini Giulia Fani Cristina Cecchi Fabrizio Chiti |
| author_facet | Elham Rezvani Boroujeni Seyed Masoud Hosseini Giulia Fani Cristina Cecchi Fabrizio Chiti |
| author_sort | Elham Rezvani Boroujeni |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most prevalent form of dementia and soluble amyloid β (Aβ) oligomers are thought to play a critical role in AD pathogenesis. Cellular prion protein (PrP<sup>C</sup>) is a high-affinity receptor for Aβ oligomers and mediates some of their toxic effects. The <i>N</i>-terminal region of PrP<sup>C</sup> can interact with Aβ, particularly the region encompassing residues 95–110. In this study, we identified a soluble and unstructured prion-derived peptide (PrP<sub>107–120</sub>) that is external to this region of the sequence and was found to successfully reduce the mitochondrial impairment, intracellular ROS generation and cytosolic Ca<sup>2+</sup> uptake induced by oligomeric Aβ<sub>42</sub> ADDLs in neuroblastoma SH-SY5Y cells. PrP<sub>107–120</sub> was also found to rescue SH-SY5Y cells from Aβ<sub>42</sub> ADDL internalization. The peptide did not change the structure and aggregation pathway of Aβ<sub>42</sub> ADDLs, did not show co-localization with Aβ<sub>42</sub> ADDLs in the cells and showed a partial colocalization with the endogenous cellular PrP<sup>C</sup>. As a sequence region that is not involved in Aβ binding but in PrP self-recognition, the peptide was suggested to protect against the toxicity of Aβ<sub>42</sub> oligomers by interfering with cellular PrP<sup>C</sup> and/or activating a signaling that protected the cells. These results strongly suggest that PrP<sub>107–120</sub> has therapeutic potential for AD. |
| first_indexed | 2024-03-10T15:53:35Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:53:35Z |
| publishDate | 2020-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-18bf68d32595473bb3e84bfd5558ea0f2023-11-20T15:48:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012119727310.3390/ijms21197273Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s DiseaseElham Rezvani Boroujeni0Seyed Masoud Hosseini1Giulia Fani2Cristina Cecchi3Fabrizio Chiti4Department of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran 1983969411, IranDepartment of Microbiology and Microbial Biotechnology, Faculty of Life Science and Biotechnology, Shahid Beheshti University, Tehran 1983969411, IranDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B Morgagni 50, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B Morgagni 50, 50134 Florence, ItalyDepartment of Experimental and Clinical Biomedical Sciences, University of Florence, Viale G.B Morgagni 50, 50134 Florence, ItalyAlzheimer’s disease (AD) is the most prevalent form of dementia and soluble amyloid β (Aβ) oligomers are thought to play a critical role in AD pathogenesis. Cellular prion protein (PrP<sup>C</sup>) is a high-affinity receptor for Aβ oligomers and mediates some of their toxic effects. The <i>N</i>-terminal region of PrP<sup>C</sup> can interact with Aβ, particularly the region encompassing residues 95–110. In this study, we identified a soluble and unstructured prion-derived peptide (PrP<sub>107–120</sub>) that is external to this region of the sequence and was found to successfully reduce the mitochondrial impairment, intracellular ROS generation and cytosolic Ca<sup>2+</sup> uptake induced by oligomeric Aβ<sub>42</sub> ADDLs in neuroblastoma SH-SY5Y cells. PrP<sub>107–120</sub> was also found to rescue SH-SY5Y cells from Aβ<sub>42</sub> ADDL internalization. The peptide did not change the structure and aggregation pathway of Aβ<sub>42</sub> ADDLs, did not show co-localization with Aβ<sub>42</sub> ADDLs in the cells and showed a partial colocalization with the endogenous cellular PrP<sup>C</sup>. As a sequence region that is not involved in Aβ binding but in PrP self-recognition, the peptide was suggested to protect against the toxicity of Aβ<sub>42</sub> oligomers by interfering with cellular PrP<sup>C</sup> and/or activating a signaling that protected the cells. These results strongly suggest that PrP<sub>107–120</sub> has therapeutic potential for AD.https://www.mdpi.com/1422-0067/21/19/7273Alzheimer’s diseaseprion peptideAβ oligomersADDLs |
| spellingShingle | Elham Rezvani Boroujeni Seyed Masoud Hosseini Giulia Fani Cristina Cecchi Fabrizio Chiti Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease International Journal of Molecular Sciences Alzheimer’s disease prion peptide Aβ oligomers ADDLs |
| title | Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease |
| title_full | Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease |
| title_fullStr | Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease |
| title_full_unstemmed | Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease |
| title_short | Soluble Prion Peptide 107–120 Protects Neuroblastoma SH-SY5Y Cells against Oligomers Associated with Alzheimer’s Disease |
| title_sort | soluble prion peptide 107 120 protects neuroblastoma sh sy5y cells against oligomers associated with alzheimer s disease |
| topic | Alzheimer’s disease prion peptide Aβ oligomers ADDLs |
| url | https://www.mdpi.com/1422-0067/21/19/7273 |
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