Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer’s Disease
dc.contributor.author | Michalska Dziama, Patrycja | |
dc.contributor.author | Mayo, Paloma | |
dc.contributor.author | Fernández-Mendívil, Cristina | |
dc.contributor.author | Tenti, Giammarco | |
dc.contributor.author | Duarte, Pablo | |
dc.contributor.author | Buendia, Izaskun | |
dc.contributor.author | Ramos García, María Teresa | |
dc.contributor.author | López, Manuela G. | |
dc.contributor.author | Menéndez Ramos, José Carlos | |
dc.contributor.author | León, Rafael | |
dc.contributor.author | León Martínez, Rafael | |
dc.date.accessioned | 2024-01-31T12:44:43Z | |
dc.date.available | 2024-01-31T12:44:43Z | |
dc.date.issued | 2020-07-22 | |
dc.description.abstract | Alzheimer’s disease is a chronic and irreversible pathological process that has become the most prevalent neurodegenerative disease. Currently, it is considered a multifactorial disease where oxidative stress and chronic neuroinflammation play a crucial role in its onset and development. Its characteristic neuronal loss has been related to the formation of neurofibrillary tangles mainly composed by hyperphosphorylated tau protein. Hyperphosphorylation of tau protein is related to the over-activity of GSK-3β, a kinase that participates in several pathological mechanisms including neuroinflammation. Neuronal loss is also related to cytosolic Ca2+ homeostasis dysregulation that triggers apoptosis and free radicals production, contributing to oxidative damage and, finally, neuronal death. Under these premises, we have obtained a new family of 4,7-dihydro-2H-pyrazolo[3–b]pyridines as multitarget directed ligands showing potent antioxidant properties and able to scavenge both oxygen and nitrogen radical species, and also, with anti-inflammatory properties. Further characterization has demonstrated their capacity to inhibit GSK-3β and to block L-type voltage dependent calcium channels. Novel derivatives have also demonstrated an interesting neuroprotective profile on in vitro models of neurodegeneration. Finally, compound 4g revokes cellular death induced by tau hyperphosphorylation in hippocampal slices by blocking reactive oxygen species (ROS) production. In conclusion, the multitarget profile exhibited by these compounds is a novel therapeutic strategy of potential interest in the search of novel treatments for Alzheimer’s disease. | |
dc.description.department | Depto. de Química en Ciencias Farmacéuticas | |
dc.description.faculty | Fac. de Farmacia | |
dc.description.refereed | TRUE | |
dc.description.sponsorship | Ministerio de Educación, Cultura y Deporte(España) | |
dc.description.sponsorship | Universidad Autónoma de Madrid | |
dc.description.sponsorship | Universidad Complutense de Madrid | |
dc.description.status | pub | |
dc.identifier.doi | 10.3390/antiox9080650 | |
dc.identifier.officialurl | https://doi.org/10.3390/antiox9080650 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/97150 | |
dc.issue.number | 8 | |
dc.journal.title | Antioxidants | |
dc.language.iso | eng | |
dc.page.initial | 650 | |
dc.page.total | 20 | |
dc.relation.projectID | info:eu-repo/grantAgreement/13/03737 | |
dc.relation.projectID | info:eu-repo/grantAgreement/16/03977 | |
dc.relation.projectID | info:eu-repo/grantAgreement/15/03269 | |
dc.relation.projectID | info:eu-repo/grantAgreement/FJCI-2016/28282 | |
dc.rights | Attribution 4.0 International | |
dc.rights.accessRights | open access | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject.cdu | 615:54 | |
dc.subject.cdu | 615.31 | |
dc.subject.keyword | Alzheimer’s disease | |
dc.subject.keyword | Anti-inflammatory drugs | |
dc.subject.keyword | Multitarget drugs | |
dc.subject.keyword | 4,7-dihydro-2H-pyrazolo[3,4-b]pyridines | |
dc.subject.keyword | GSK-3β inhibitor | |
dc.subject.keyword | Voltage gated calcium channels antagonists | |
dc.subject.keyword | Neuroprotection | |
dc.subject.ucm | Ciencias Biomédicas | |
dc.subject.unesco | 24 Ciencias de la Vida | |
dc.title | Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer’s Disease | |
dc.type | journal article | |
dc.volume.number | 9 | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 298927e3-bd5b-46ad-bdbe-b818ade8cfb1 | |
relation.isAuthorOfPublication | 294d039a-95b4-47a5-ac94-510ba921fd75 | |
relation.isAuthorOfPublication | a364ae2f-f011-462f-8c10-fa9999e46724 | |
relation.isAuthorOfPublication | 4c8ca147-677d-4846-97b7-d4419662ff60 | |
relation.isAuthorOfPublication | 7093c6ce-e368-44f0-a993-8f7212cb1c2a | |
relation.isAuthorOfPublication.latestForDiscovery | 298927e3-bd5b-46ad-bdbe-b818ade8cfb1 |
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