Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells
Alzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. U...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13461 |
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| author | Jessica Maiuolo Paola Costanzo Mariorosario Masullo Antonio D’Errico Rosarita Nasso Sonia Bonacci Vincenzo Mollace Manuela Oliverio Rosaria Arcone |
| author_facet | Jessica Maiuolo Paola Costanzo Mariorosario Masullo Antonio D’Errico Rosarita Nasso Sonia Bonacci Vincenzo Mollace Manuela Oliverio Rosaria Arcone |
| author_sort | Jessica Maiuolo |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important trophic and antioxidant roles, while their massive presence leads to a cascade of events culminating in the onset of AD. The fibrils of beta-amyloid proteins are formed by the process of fibrillogenesis that, starting from individual monomers of beta-amyloid, can generate polymers of this protein, constituting the hypothesis of the “amyloid cascade”. To date, due to the lack of pharmacological treatment for AD without toxic side effects, chemical research is directed towards the realization of hybrid compounds that can act as an adjuvant in the treatment of this neurodegenerative pathology. The hybrid compounds used in this work include moieties of a hydroxytyrosol, a nitrohydroxytyrosol, a tyrosol, and a homovanillyl alcohol bound to the N-benzylpiperidine moiety of donepezil, the main drug used in AD. Previous experiments have shown different properties of these hybrids, including low toxicity and antioxidant and chelating activities. The purpose of this work was to test the effects of hybrid compounds mixed with A<i>β</i> <sub>1–40</sub> to induce fibrillogenesis and mimic AD pathogenesis. This condition has been studied both in test tubes and by an in vitro model of neuronal differentiated human SH-SY5Y neuroblastoma cells. The results obtained from test tube experiments showed that some hybrids inhibit the activity of the enzymes AChE, BuChE, and BACE-1. Cell experiments suggested that hybrids could inhibit fibrillogenesis, negatively modulating caspase-3. They were also shown to exert antioxidant effects, and the acetylated hybrids were found to be more functional and efficient than nonacetylated forms. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:38Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-95733cf32c064a06a56ec350197c712e2023-11-19T08:17:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171346110.3390/ijms241713461Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma CellsJessica Maiuolo0Paola Costanzo1Mariorosario Masullo2Antonio D’Errico3Rosarita Nasso4Sonia Bonacci5Vincenzo Mollace6Manuela Oliverio7Rosaria Arcone8Department of Health Science, Institute of Research for Food Safety & Health (IRC-FSH), University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci, Cubo 12C, 87036 Rende, ItalyDepartment of Movement Science and Well-Being, University “Parthenope” of Naples, Via Medina, 40, 80133 Napoli, ItalyDepartment of Movement Science and Well-Being, University “Parthenope” of Naples, Via Medina, 40, 80133 Napoli, ItalyDepartment of Movement Science and Well-Being, University “Parthenope” of Naples, Via Medina, 40, 80133 Napoli, ItalyDepartment of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Health Science, Institute of Research for Food Safety & Health (IRC-FSH), University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Movement Science and Well-Being, University “Parthenope” of Naples, Via Medina, 40, 80133 Napoli, ItalyAlzheimer’s disease (AD) is the most common neurodegenerative pathology among progressive dementias, and it is characterized by the accumulation in the brain of extracellular aggregates of beta-amyloid proteins and neurofibrillary intracellular tangles consisting of τ-hyperphosphorylated proteins. Under normal conditions, beta-amyloid peptides exert important trophic and antioxidant roles, while their massive presence leads to a cascade of events culminating in the onset of AD. The fibrils of beta-amyloid proteins are formed by the process of fibrillogenesis that, starting from individual monomers of beta-amyloid, can generate polymers of this protein, constituting the hypothesis of the “amyloid cascade”. To date, due to the lack of pharmacological treatment for AD without toxic side effects, chemical research is directed towards the realization of hybrid compounds that can act as an adjuvant in the treatment of this neurodegenerative pathology. The hybrid compounds used in this work include moieties of a hydroxytyrosol, a nitrohydroxytyrosol, a tyrosol, and a homovanillyl alcohol bound to the N-benzylpiperidine moiety of donepezil, the main drug used in AD. Previous experiments have shown different properties of these hybrids, including low toxicity and antioxidant and chelating activities. The purpose of this work was to test the effects of hybrid compounds mixed with A<i>β</i> <sub>1–40</sub> to induce fibrillogenesis and mimic AD pathogenesis. This condition has been studied both in test tubes and by an in vitro model of neuronal differentiated human SH-SY5Y neuroblastoma cells. The results obtained from test tube experiments showed that some hybrids inhibit the activity of the enzymes AChE, BuChE, and BACE-1. Cell experiments suggested that hybrids could inhibit fibrillogenesis, negatively modulating caspase-3. They were also shown to exert antioxidant effects, and the acetylated hybrids were found to be more functional and efficient than nonacetylated forms.https://www.mdpi.com/1422-0067/24/17/13461Alzheimer’s disease (AD)donepezilhybrid compoundspolyphenolsBACE-1fibrillogenesis |
| spellingShingle | Jessica Maiuolo Paola Costanzo Mariorosario Masullo Antonio D’Errico Rosarita Nasso Sonia Bonacci Vincenzo Mollace Manuela Oliverio Rosaria Arcone Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells International Journal of Molecular Sciences Alzheimer’s disease (AD) donepezil hybrid compounds polyphenols BACE-1 fibrillogenesis |
| title | Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells |
| title_full | Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells |
| title_fullStr | Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells |
| title_full_unstemmed | Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells |
| title_short | Hydroxytyrosol–Donepezil Hybrids Play a Protective Role in an In Vitro Induced Alzheimer’s Disease Model and in Neuronal Differentiated Human SH-SY5Y Neuroblastoma Cells |
| title_sort | hydroxytyrosol donepezil hybrids play a protective role in an in vitro induced alzheimer s disease model and in neuronal differentiated human sh sy5y neuroblastoma cells |
| topic | Alzheimer’s disease (AD) donepezil hybrid compounds polyphenols BACE-1 fibrillogenesis |
| url | https://www.mdpi.com/1422-0067/24/17/13461 |
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