Griñán Ferré, ChristianMarsal García, LauraBellver Sanchis, AinaKondengaden, Shukkoor MuhammedTurga, Ravi ChakraVázquez Cruz, SantiagoPallàs i Llibería, Mercè, 1964-2021-03-252021-03-252019-12-151945-4589https://hdl.handle.net/2445/175749The 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.18 p.application/pdfengcc-by (c) Griñán Ferré, Christian et al., 2019http://creativecommons.org/licenses/by/3.0/esMalaltia d'AlzheimerInflamacióEstrès oxidatiuAlzheimer's diseaseInflammationOxidative stressinfo:eu-repo/semantics/article7076262021-03-25info:eu-repo/semantics/openAccess31804189