Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK
Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative...
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MDPI AG
2022-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/8/2009 |
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| author | Vincenzo Vestuto Giuseppina Amodio Giacomo Pepe Manuela Giovanna Basilicata Raffaella Belvedere Enza Napolitano Daniela Guarnieri Valentina Pagliara Simona Paladino Manuela Rodriquez Alessia Bertamino Pietro Campiglia Paolo Remondelli Ornella Moltedo |
| author_facet | Vincenzo Vestuto Giuseppina Amodio Giacomo Pepe Manuela Giovanna Basilicata Raffaella Belvedere Enza Napolitano Daniela Guarnieri Valentina Pagliara Simona Paladino Manuela Rodriquez Alessia Bertamino Pietro Campiglia Paolo Remondelli Ornella Moltedo |
| author_sort | Vincenzo Vestuto |
| collection | DOAJ |
| description | Parkinson’s disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson’s disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD. |
| first_indexed | 2024-03-09T04:40:09Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T04:40:09Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8273afd6b2414f98a31c9f0baef5e4d52023-12-03T13:22:09ZengMDPI AGBiomedicines2227-90592022-08-01108200910.3390/biomedicines10082009Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERKVincenzo Vestuto0Giuseppina Amodio1Giacomo Pepe2Manuela Giovanna Basilicata3Raffaella Belvedere4Enza Napolitano5Daniela Guarnieri6Valentina Pagliara7Simona Paladino8Manuela Rodriquez9Alessia Bertamino10Pietro Campiglia11Paolo Remondelli12Ornella Moltedo13Department of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, I-84034 Baronissi-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Chemistry and Biology, I-84034 Fisciano-Salerno, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, I-84034 Baronissi-Salerno, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, I-80131 Naples, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyDepartment of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, I-84034 Baronissi-Salerno, ItalyDepartment of Pharmacy, University of Salerno, I-84034 Fisciano-Salerno, ItalyParkinson’s disease (PD) represents one of the most common neurodegenerative disorders, characterized by a dopamine (DA) deficiency in striatal synapses and misfolded toxic α-synuclein aggregates with concomitant cytotoxicity. In this regard, the misfolded proteins accumulation in neurodegenerative disorders induces a remarkable perturbations of endoplasmic reticulum (ER) homeostasis leading to persistent ER stress, which in turn, effects protein synthesis, modification, and folding quality control. A large body of evidence suggests that natural products target the ER stress signaling pathway, exerting a potential action in cancers, diabetes, cardiovascular and neurodegenerative diseases. This study aims to assess the neuroprotective effect of cocoa extract and its purified fractions against a cellular model of Parkinson’s disease represented by 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma. Our findings demonstrate, for the first time, the ability of cocoa to specifically targets PERK sensor, with significant antioxidant and antiapoptotic activities as both crude and fractioning extracts. In addition, cocoa also showed antiapoptotic properties in 3D cell model and a notable ability to inhibit the accumulation of α-synuclein in 6-OHDA-induced cells. Overall, these results indicate that cocoa exerts neuroprotective effects suggesting a novel possible strategy to prevent or, at least, mitigate neurodegenerative disorders, such as PD.https://www.mdpi.com/2227-9059/10/8/2009Parkinson’s diseaseunfolded protein responseendoplasmic reticulum stressPERKoxidative stresscocoa |
| spellingShingle | Vincenzo Vestuto Giuseppina Amodio Giacomo Pepe Manuela Giovanna Basilicata Raffaella Belvedere Enza Napolitano Daniela Guarnieri Valentina Pagliara Simona Paladino Manuela Rodriquez Alessia Bertamino Pietro Campiglia Paolo Remondelli Ornella Moltedo Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK Biomedicines Parkinson’s disease unfolded protein response endoplasmic reticulum stress PERK oxidative stress cocoa |
| title | Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK |
| title_full | Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK |
| title_fullStr | Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK |
| title_full_unstemmed | Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK |
| title_short | Cocoa Extract Provides Protection against 6-OHDA Toxicity in SH-SY5Y Dopaminergic Neurons by Targeting PERK |
| title_sort | cocoa extract provides protection against 6 ohda toxicity in sh sy5y dopaminergic neurons by targeting perk |
| topic | Parkinson’s disease unfolded protein response endoplasmic reticulum stress PERK oxidative stress cocoa |
| url | https://www.mdpi.com/2227-9059/10/8/2009 |
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