Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors
Alzheimer’s disease is a memory-related neurodegenerative condition leading to cognitive impairment. Cholinergic deficit, together with other underlying mechanisms, leads the to onset and progression of the disease. Consequently, acetylcholinesterase inhibitors are used for the symptomatic treatment...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Applied Sciences |
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| Online Access: | https://www.mdpi.com/2076-3417/11/11/5044 |
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| author | Giovanni Ribaudo Maurizio Memo Alessandra Gianoncelli |
| author_facet | Giovanni Ribaudo Maurizio Memo Alessandra Gianoncelli |
| author_sort | Giovanni Ribaudo |
| collection | DOAJ |
| description | Alzheimer’s disease is a memory-related neurodegenerative condition leading to cognitive impairment. Cholinergic deficit, together with other underlying mechanisms, leads the to onset and progression of the disease. Consequently, acetylcholinesterase inhibitors are used for the symptomatic treatment of dementia, even if limited efficacy is observed. More recently, some specific phosphodiesterase isoforms emerged as promising, alternative targets for developing inhibitors to contrast neurodegeneration. Phosphodiesterase isoforms 4, 5 and 9 were found to be expressed in brain regions that are relevant for cognition. Given the complex nature of Alzheimer’s disease and the combination of involved biochemical mechanisms, the development of polypharmacological agents acting on more than one pathway is desirable. This review provides an overview of recent reports focused on natural and Nature-inspired small molecules, or plant extracts, acting as dual cholinesterase and phosphodiesterase inhibitors. In the context of the multi-target directed ligand approach, such molecules would pave the way for the development of novel agents against neurodegeneration. More precisely, according to the literature data, xanthines, other alkaloids, flavonoids, coumarins and polyphenolic acids represent promising scaffolds for future optimization. |
| first_indexed | 2024-03-10T10:53:39Z |
| format | Article |
| id | doaj.art-6db4b7a6806246d8849a5116cdfeb92e |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T10:53:39Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-6db4b7a6806246d8849a5116cdfeb92e2023-11-21T22:00:50ZengMDPI AGApplied Sciences2076-34172021-05-011111504410.3390/app11115044Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase InhibitorsGiovanni Ribaudo0Maurizio Memo1Alessandra Gianoncelli2Department of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, ItalyDepartment of Molecular and Translational Medicine, University of Brescia, 25121 Brescia, ItalyAlzheimer’s disease is a memory-related neurodegenerative condition leading to cognitive impairment. Cholinergic deficit, together with other underlying mechanisms, leads the to onset and progression of the disease. Consequently, acetylcholinesterase inhibitors are used for the symptomatic treatment of dementia, even if limited efficacy is observed. More recently, some specific phosphodiesterase isoforms emerged as promising, alternative targets for developing inhibitors to contrast neurodegeneration. Phosphodiesterase isoforms 4, 5 and 9 were found to be expressed in brain regions that are relevant for cognition. Given the complex nature of Alzheimer’s disease and the combination of involved biochemical mechanisms, the development of polypharmacological agents acting on more than one pathway is desirable. This review provides an overview of recent reports focused on natural and Nature-inspired small molecules, or plant extracts, acting as dual cholinesterase and phosphodiesterase inhibitors. In the context of the multi-target directed ligand approach, such molecules would pave the way for the development of novel agents against neurodegeneration. More precisely, according to the literature data, xanthines, other alkaloids, flavonoids, coumarins and polyphenolic acids represent promising scaffolds for future optimization.https://www.mdpi.com/2076-3417/11/11/5044Alzheimer’s diseaseacetylcholinesterasephosphodiesterasemulti-target directed ligandpolypharmacologynatural compounds |
| spellingShingle | Giovanni Ribaudo Maurizio Memo Alessandra Gianoncelli Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors Applied Sciences Alzheimer’s disease acetylcholinesterase phosphodiesterase multi-target directed ligand polypharmacology natural compounds |
| title | Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors |
| title_full | Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors |
| title_fullStr | Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors |
| title_full_unstemmed | Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors |
| title_short | Multi-target Natural and Nature-Inspired Compounds against Neurodegeneration: A Focus on Dual Cholinesterase and Phosphodiesterase Inhibitors |
| title_sort | multi target natural and nature inspired compounds against neurodegeneration a focus on dual cholinesterase and phosphodiesterase inhibitors |
| topic | Alzheimer’s disease acetylcholinesterase phosphodiesterase multi-target directed ligand polypharmacology natural compounds |
| url | https://www.mdpi.com/2076-3417/11/11/5044 |
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