Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease
Alzheimer’s disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegene...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2447 |
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| author | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Lola Corzo Ramón Cacabelos |
| author_facet | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Lola Corzo Ramón Cacabelos |
| author_sort | Olaia Martínez-Iglesias |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegenerative disorders. Targeting the epigenetic apparatus with bioactive compounds (epidrugs) may aid AD prevention treatment. The aims of this study were to determine the composition of a porcine brain-derived extract Nosustrophine, and whether treating young and older trigenic AD mice produced targeted epigenetic and neuroprotective effects against neurodegeneration. Nosustrophine regulated AD-related <i>APOE</i> and <i>PSEN2</i> gene expression in young and older APP/BIN1/COPS5 mice, inflammation-related (<i>NOS3</i> and <i>COX-2</i>) gene expression in 3–4-month-old mice only, global (5mC)- and de novo DNA methylation (<i>DNMT3a</i>), <i>HDAC3</i> expression and HDAC activity in 3–4-month-old mice; and <i>SIRT1</i> expression and acetylated histone H3 protein levels in 8–9-month-old mice. Mass spectrometric analysis of Nosustrophine extracts revealed the presence of adenosylhomocysteinase, an enzyme implicated in DNA methylation, and nicotinamide phosphoribosyltransferase, which produces the NAD+ precursor, enhancing SIRT1 activity. Our findings show that Nosustrophine exerts substantial epigenetic effects against AD-related neurodegeneration and establishes Nosustrophine as a novel nutraceutical bioproduct with epigenetic properties (epinutraceutical) that may be therapeutically effective for prevention and early treatment for AD-related neurodegeneration. |
| first_indexed | 2024-03-09T18:04:32Z |
| format | Article |
| id | doaj.art-050cd66424584882b2bcf86c5768e880 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:04:32Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-050cd66424584882b2bcf86c5768e8802023-11-24T09:35:59ZengMDPI AGPharmaceutics1999-49232022-11-011411244710.3390/pharmaceutics14112447Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s DiseaseOlaia Martínez-Iglesias0Vinogran Naidoo1Iván Carrera2Lola Corzo3Ramón Cacabelos4EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainAlzheimer’s disease (AD), the most common cause of dementia, causes irreversible memory loss and cognitive deficits. Current AD drugs do not significantly improve cognitive function or cure the disease. Novel bioproducts are promising options for treating a variety of diseases, including neurodegenerative disorders. Targeting the epigenetic apparatus with bioactive compounds (epidrugs) may aid AD prevention treatment. The aims of this study were to determine the composition of a porcine brain-derived extract Nosustrophine, and whether treating young and older trigenic AD mice produced targeted epigenetic and neuroprotective effects against neurodegeneration. Nosustrophine regulated AD-related <i>APOE</i> and <i>PSEN2</i> gene expression in young and older APP/BIN1/COPS5 mice, inflammation-related (<i>NOS3</i> and <i>COX-2</i>) gene expression in 3–4-month-old mice only, global (5mC)- and de novo DNA methylation (<i>DNMT3a</i>), <i>HDAC3</i> expression and HDAC activity in 3–4-month-old mice; and <i>SIRT1</i> expression and acetylated histone H3 protein levels in 8–9-month-old mice. Mass spectrometric analysis of Nosustrophine extracts revealed the presence of adenosylhomocysteinase, an enzyme implicated in DNA methylation, and nicotinamide phosphoribosyltransferase, which produces the NAD+ precursor, enhancing SIRT1 activity. Our findings show that Nosustrophine exerts substantial epigenetic effects against AD-related neurodegeneration and establishes Nosustrophine as a novel nutraceutical bioproduct with epigenetic properties (epinutraceutical) that may be therapeutically effective for prevention and early treatment for AD-related neurodegeneration.https://www.mdpi.com/1999-4923/14/11/2447Alzheimer’s diseaseDNA methylationepinutraceuticalHDACPSEN2Sirtuin |
| spellingShingle | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Lola Corzo Ramón Cacabelos Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease Pharmaceutics Alzheimer’s disease DNA methylation epinutraceutical HDAC PSEN2 Sirtuin |
| title | Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease |
| title_full | Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease |
| title_fullStr | Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease |
| title_full_unstemmed | Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease |
| title_short | Nosustrophine: An Epinutraceutical Bioproduct with Effects on DNA Methylation, Histone Acetylation and Sirtuin Expression in Alzheimer’s Disease |
| title_sort | nosustrophine an epinutraceutical bioproduct with effects on dna methylation histone acetylation and sirtuin expression in alzheimer s disease |
| topic | Alzheimer’s disease DNA methylation epinutraceutical HDAC PSEN2 Sirtuin |
| url | https://www.mdpi.com/1999-4923/14/11/2447 |
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