Abstract: Alzheimer’s disease (AD) is the most prevalent form of dementia and soluble amyloid beta (Abeta) oligomers are thought to play a critical role in AD pathogenesis. Cellular prion protein (PrPC) is a high-affinity receptor for Abeta oligomers and mediates some of their toxic effects. The N-terminal region of PrPC can interact with Abeta, particularly the region encompassing residues 95–110. In this study, we identified a soluble and unstructured prion-derived peptide (PrP107–120) that is external to this region of the sequence and was found to successfully reduce the mitochondrial impairment, intracellular ROS generation and cytosolic Ca2+ uptake induced by oligomeric Abeta42 ADDLs in neuroblastoma SH-SY5Y cells. PrP107–120 was also found to rescue SH-SY5Y cells from Abeta42 ADDL internalization. The peptide did not change the structure and aggregation pathway of Abeta42 ADDLs, did not show co-localization with Abeta42 ADDLs in the cells and showed a partial colocalization with the endogenous cellular PrPC. As a sequence region that is not involved in Abeta binding but in PrP self-recognition, the peptide was suggested to protect against the toxicity of Abeta42 oligomers by interfering with cellular PrPC and/or activating a signaling that protected the cells. These results strongly suggest that PrP107–120 has therapeutic potential for AD.

Soluble Prion peptide 107–120 protects neuroblastoma SH-SY5Y cells against oligomers associated with Alzheimer’s disease / Elham Rezvani Boroujeni, Seyed Masoud Hosseini, Giulia Fani, Cristina Cecchi, Fabrizio Chiti. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 21:(2020), pp. 7273-7294. [10.3390/ijms21197273]

Soluble Prion peptide 107–120 protects neuroblastoma SH-SY5Y cells against oligomers associated with Alzheimer’s disease

Giulia Fani
Investigation
;
Cristina Cecchi
Conceptualization
;
Fabrizio Chiti
Supervision
2020

Abstract

Abstract: Alzheimer’s disease (AD) is the most prevalent form of dementia and soluble amyloid beta (Abeta) oligomers are thought to play a critical role in AD pathogenesis. Cellular prion protein (PrPC) is a high-affinity receptor for Abeta oligomers and mediates some of their toxic effects. The N-terminal region of PrPC can interact with Abeta, particularly the region encompassing residues 95–110. In this study, we identified a soluble and unstructured prion-derived peptide (PrP107–120) that is external to this region of the sequence and was found to successfully reduce the mitochondrial impairment, intracellular ROS generation and cytosolic Ca2+ uptake induced by oligomeric Abeta42 ADDLs in neuroblastoma SH-SY5Y cells. PrP107–120 was also found to rescue SH-SY5Y cells from Abeta42 ADDL internalization. The peptide did not change the structure and aggregation pathway of Abeta42 ADDLs, did not show co-localization with Abeta42 ADDLs in the cells and showed a partial colocalization with the endogenous cellular PrPC. As a sequence region that is not involved in Abeta binding but in PrP self-recognition, the peptide was suggested to protect against the toxicity of Abeta42 oligomers by interfering with cellular PrPC and/or activating a signaling that protected the cells. These results strongly suggest that PrP107–120 has therapeutic potential for AD.
2020
21
7273
7294
Goal 3: Good health and well-being for people
Elham Rezvani Boroujeni, Seyed Masoud Hosseini, Giulia Fani, Cristina Cecchi, Fabrizio Chiti
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1213415
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