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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/175749
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
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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.
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GRIÑÁN FERRÉ, Christian, MARSAL GARCÍA, Laura, BELLVER SANCHIS, Aina, KONDENGADEN, Shukkoor muhammed, TURGA, Ravi chakra, VÁZQUEZ CRUZ, Santiago, PALLÀS I LLIBERÍA, Mercè. 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. _Aging_. 2019. Vol. 11, núm. 23, pàgs. 11591-11608. [consulta: 26 de gener de 2026]. ISSN: 1945-4589. [Disponible a: https://hdl.handle.net/2445/175749]