A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide
Investigating amyloid–β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1–42) peptide to misfold in solution, correlated to the aetiology of Alzheime...
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2025-01-01
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| author | Angelo Santoro Antonio Ricci Manuela Rodriquez Michela Buonocore Anna Maria D’Ursi |
| author_facet | Angelo Santoro Antonio Ricci Manuela Rodriquez Michela Buonocore Anna Maria D’Ursi |
| author_sort | Angelo Santoro |
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| description | Investigating amyloid–β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1–42) peptide to misfold in solution, correlated to the aetiology of Alzheimer’s disease (AD), is one of the main hindrances to characterising its aggregation kinetics in a cell-mimetic environment. Moreover, the Aβ(1–42) aggregation triggers the unfolded protein response (UPR) in the endoplasmic reticulum (ER), leading to cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage cellular components and trigger inflammation. Antioxidants like curcumin, a derivative of Curcuma longa, help mitigate ER stress by scavenging ROS and enhancing antioxidant enzymes. Furthermore, evidence in the literature highlights the effect of curcumin on the secondary structure of Aβ(1–42). This explorative study investigates the Aβ(1–42) peptide conformational behaviour in the presence of curcumin and six derivatives using circular dichroism (CD) to explore their interactions with lipid bilayers, potentially preventing aggregate formation. The results suggest that the synthetic tetrahydrocurcumin (THC) derivative interacts with the amyloid peptide in all the systems presented, while cyclocurcumin (CYC) and bisdemethoxycurcumin (BMDC) only interact when the peptide is in a less stable conformation. Molecular dynamics simulations helped visualise the curcuminoids’ effect in an aqueous system and hypothesise the importance of the peptide surface exposition to the solvent, differently modulated by the curcumin derivatives. |
| format | Article |
| id | doaj-art-614cc13b11c0438c8adf6d1b7b185609 |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Antioxidants |
| spelling | doaj-art-614cc13b11c0438c8adf6d1b7b1856092025-01-24T13:19:19ZengMDPI AGAntioxidants2076-39212025-01-011415310.3390/antiox14010053A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid PeptideAngelo Santoro0Antonio Ricci1Manuela Rodriquez2Michela Buonocore3Anna Maria D’Ursi4Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyFresenius Kabi iPSUM, Via San Leonardo, 23, 45010 Villadose, ItalyDepartment of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyDepartment of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, ItalyInvestigating amyloid–β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1–42) peptide to misfold in solution, correlated to the aetiology of Alzheimer’s disease (AD), is one of the main hindrances to characterising its aggregation kinetics in a cell-mimetic environment. Moreover, the Aβ(1–42) aggregation triggers the unfolded protein response (UPR) in the endoplasmic reticulum (ER), leading to cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage cellular components and trigger inflammation. Antioxidants like curcumin, a derivative of Curcuma longa, help mitigate ER stress by scavenging ROS and enhancing antioxidant enzymes. Furthermore, evidence in the literature highlights the effect of curcumin on the secondary structure of Aβ(1–42). This explorative study investigates the Aβ(1–42) peptide conformational behaviour in the presence of curcumin and six derivatives using circular dichroism (CD) to explore their interactions with lipid bilayers, potentially preventing aggregate formation. The results suggest that the synthetic tetrahydrocurcumin (THC) derivative interacts with the amyloid peptide in all the systems presented, while cyclocurcumin (CYC) and bisdemethoxycurcumin (BMDC) only interact when the peptide is in a less stable conformation. Molecular dynamics simulations helped visualise the curcuminoids’ effect in an aqueous system and hypothesise the importance of the peptide surface exposition to the solvent, differently modulated by the curcumin derivatives.https://www.mdpi.com/2076-3921/14/1/53Alzheimer’s diseasecurcuminantioxidantsendoplasmic reticulum stressunfolded protein responsecircular dichroism |
| spellingShingle | Angelo Santoro Antonio Ricci Manuela Rodriquez Michela Buonocore Anna Maria D’Ursi A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide Antioxidants Alzheimer’s disease curcumin antioxidants endoplasmic reticulum stress unfolded protein response circular dichroism |
| title | A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide |
| title_full | A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide |
| title_fullStr | A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide |
| title_full_unstemmed | A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide |
| title_short | A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1–42) Amyloid Peptide |
| title_sort | structural effect of the antioxidant curcuminoids on the aβ 1 42 amyloid peptide |
| topic | Alzheimer’s disease curcumin antioxidants endoplasmic reticulum stress unfolded protein response circular dichroism |
| url | https://www.mdpi.com/2076-3921/14/1/53 |
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