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https://hdl.handle.net/2445/175749
Title: | Pharmacological inhibition of G9a/GLP restores cognition and reduces oxidative stress, neuroinflammation and β-Amyloid plaques in an early-onset Alzheimer's disease mouse model |
Author: | Griñán Ferré, Christian Marsal García, Laura Bellver Sanchis, Aina, Kondengaden, Shukkoor Muhammed Turga, Ravi Chakra Vázquez Cruz, Santiago Pallàs i Llibería, Mercè, 1964- |
Keywords: | Malaltia d'Alzheimer Inflamació Estrès oxidatiu Alzheimer's disease Inflammation Oxidative stress |
Issue Date: | 15-Dec-2019 |
Publisher: | Impact Journals |
Abstract: | The implication of epigenetic mechanisms in Alzheimer's disease (AD) has been demonstrated in several studies. UNC0642, a specific and potent inhibitor of methyltransferase activity G9a/GLP (G9a-like) complex, was evaluated in the 5XFAD mouse model. UNC0642 treatment rescued 5XFAD cognition impairment, reduced DNAmethylation (5-mC), increased hydroxymethylation (5-hmC), and decreased the di-methylation of lysine 9 of histone H3 (H3K9me2) levels in the hippocampus. Increases in the Nuclear Factor erythroid-2-Related Factor 2 (NRF2), Heme oxygenase decycling 1 (Hmox1) gene expression, and diminution in Reactive Oxygen Species (ROS) were also reported. Moreover, neuroinflammatory markers, such as Interleukin 6 (Il-6), Tumor necrosis factor-alpha (Tnf-α) gene expression, and Glial fibrillary acidic protein (GFAP) immunofluorescence were reduced by UNC0642 treatment. An increase in Nerve growth factor (Ngf), Nerve growth factor inducible (Vgf) gene expression, Brain-derived neurotrophic factor (BDNF), and Synaptophysin (SYN) were found after UNC0642 treatment. Importantly, a reduction in β-amyloid plaques was also observed. In conclusion, our work demonstrates that the inhibition of the G9a/GLP complex by UNC0642 delivered significant neuroprotective effects in 5XFAD mice, point out G9a/GLP as a new target for AD. |
Note: | Reproducció del document publicat a: https://doi.org/10.18632/aging.102558 |
It is part of: | Aging, 2019, vol. 11, num. 23, p. 11591-11608 |
URI: | https://hdl.handle.net/2445/175749 |
Related resource: | https://doi.org/10.18632/aging.102558 |
ISSN: | 1945-4589 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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