Press Release

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

02-13-2020

The cover features Figure 7 "Scheme of epigenetic and molecular mechanisms changed in 5XFAD mice induced by pharmacological inhibition of G9a/GLP by UNC0642" from Griñán-Ferré et al.

UNC0642, a specific and potent inhibitor of methyltransferase activity G9a/GLP complex, was evaluated in the 5XFAD mouse model.

UNC0642 treatment rescued 5XFAD cognition impairment, reduced DNA-methylation, increased hydroxymethylation, and decreased the di-methylation of lysine 9 of histone H3 levels in the hippocampus.

An increase in Nerve growth factor, Nerve growth factor inducible gene expression, Brain-derived neurotrophic factor, and Synaptophysin were found after UNC0642 treatment.

Dr. Mercè Pallàs from the Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences at the Institute of Neuroscience, in the University of Barcelona (NeuroUB) said, "Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and its most significant factor is advanced age."

"Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and its most significant factor is advanced age."

- Dr. Mercè Pallàs, Pharmacology Section, Department of Pharmacology, Toxicology, and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences at the Institute of Neuroscience, in the University of Barcelona (NeuroUB)

Various mechanisms, such as DNA methylation, hydroxymethylation, histone modifications, and regulation of the non-coding RNA, regulate the accessibility of chromatin to transcription factors and, therefore, these modifications are implicated in the modulation of DNA replication, transcription, and repair.

Consequently, its dysregulation is closely related to cognitive decline in aging and transcriptional changes in various neurogenerative diseases such as AD, Huntingtons disease and Amyotrophic lateral sclerosis.

Figure 7. Scheme of epigenetic and molecular mechanisms changed in 5XFAD mice induced by pharmacological inhibition of G9a/GLP by UNC0642 "Created with BioRender.com" (A).

Those epigenetic modifications lead to transcription repression.

Of note, the critical role of epigenetics in 5XFAD was revealed in a recent study, including a correlation among cognitive impairment, A pathology, and epigenetic modifications.

The present work aimed to evaluate the beneficial effects of the pharmacological inhibition activity of G9a/GLP with UNC0642 in 5XFAD mice, evaluating epigenetic changes, cognitive improvement, and the influence of the G9a/GLP complex inhibition in amyloid pathology, OS, neuroinflammation, and neuronal plasticity.

The Pallàs Research Team concluded, "our results provide new evidence that inhibition G9a/GLP activity might be a promising target for AD therapy (Figure 7)."

Full Text - https://doi.org/10.18632/aging.102558

Correspondence to: Mercè Pallàs email: pallas@ub.edu

Keywords: G9a/GLP, epigenetics, neuroinflammation, synaptic plasticity, β-amyloid plaques

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research as well as topics beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, cancer, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR among others), and approaches to modulating these signaling pathways.

To learn more about Aging-US, please visit http://www.Aging-US.com or connect with @AgingJrnl

Aging-US is published by Impact Journals, LLC please visit http://www.ImpactJournals.com or connect with @ImpactJrnls

Media Contact
18009220957x105
MEDIA@IMPACTJOURNALS.COM