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Title: | Deletion of Gadd45a Expression in Mice Leads to Cognitive and Synaptic Impairment Associated with Alzheimer’s Disease Hallmarks. |
Author: | Griñán Ferré, Christian Jarné-Ferrer, Júlia Bellver-Sanchis, Aina Ribalta Vilella, Marta Barroso Fernández, Emma Salvador, Jesús M. Jurado Aguilar, Javier Palomer Tarridas, Francesc Xavier Vázquez Carrera, Manuel Pallàs i Llibería, Mercè, 1964- |
Keywords: | Malaltia d'Alzheimer Malalties neurodegeneratives Epigenètica Alzheimer's disease Neurodegenerative Diseases Epigenetics |
Issue Date: | 23-Feb-2024 |
Publisher: | MDPI |
Abstract: | <p><em>Gadd45 genes have been implicated in survival mechanisms, including apoptosis, autophagy,</em></p><p><em>cell cycle arrest, and DNA repair, which are processes related to aging and life span. Here, we</em></p><p><em>analyzed if the deletion of Gadd45a activates pathways involved in neurodegenerative disorders such</em></p><p><em>as Alzheimer’s Disease (AD). This study used wild-type (WT) and Gadd45a knockout (Gadd45a−/−)</em></p><p><em>mice to evaluate AD progression. Behavioral tests showed that Gadd45a−/− mice presented lower</em></p><p><em>working and spatial memory, pointing out an apparent cognitive impairment compared with WT</em></p><p><em>animals, accompanied by an increase in Tau hyperphosphorylation and the levels of kinases involved</em></p><p><em>in its phosphorylation in the hippocampus. Moreover, Gadd45a−/− animals significantly increased the</em></p><p><em>brain’s pro-inflammatory cytokines and modified autophagy markers. Notably, neurotrophins and</em></p><p><em>the dendritic spine length of the neurons were reduced in Gadd45a−/− mice, which could contribute</em></p><p><em>to the cognitive alterations observed in these animals. Overall, these findings demonstrate that the</em></p><p><em>lack of the Gadd45a gene activates several pathways that exacerbate AD pathology, suggesting that</em></p><p><em>promoting this protein’s expression or function might be a promising therapeutic strategy to slow</em></p><p><em>down AD progression.</em></p> |
Note: | Reproducció del document publicat a: |
It is part of: | International Journal of Molecular Sciences, 2024 |
URI: | http://hdl.handle.net/2445/210000 |
ISSN: | 1661-6596 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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