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Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson's disease.
Front Cell Neurosci
August 2024
Parkinson Disorders Research Laboratory, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA, United States.
Aberrant epigenetic modification has been implicated in the pathogenesis of Parkinson's disease (PD), which is characterized by the irreversible loss of dopaminergic (DAergic) neurons. However, the mechanistic landscape of histone acetylation (ac) in PD has yet to be fully explored. Herein, we mapped the proteomic acetylation profiling changes at core histones H4 and thus identified H4K12ac as a key epigenomic mark in dopaminergic neuronal cells as well as MitoPark animal model of PD.
View Article and Find Full Text PDFPromises and challenges in pharmacoepigenetics.
Camb Prism Precis Med
February 2023
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Pharmacogenetics, the study of how interindividual genetic differences affect drug response, does not explain all observed heritable variance in drug response. Epigenetic mechanisms, such as DNA methylation, and histone acetylation may account for some of the unexplained variances. Epigenetic mechanisms modulate gene expression and can be suitable drug targets and can impact the action of nonepigenetic drugs.
View Article and Find Full Text PDFThe pharmacoepigenomic landscape of cancer cell lines reveals the epigenetic component of drug sensitivity.
Commun Biol
August 2023
Computational Health Center, Helmholtz Munich, 85764, Neuherberg, Germany.
Aberrant DNA methylation accompanies genetic alterations during oncogenesis and tumour homeostasis and contributes to the transcriptional deregulation of key signalling pathways in cancer. Despite increasing efforts in DNA methylation profiling of cancer patients, there is still a lack of epigenetic biomarkers to predict treatment efficacy. To address this, we analyse 721 cancer cell lines across 22 cancer types treated with 453 anti-cancer compounds.
View Article and Find Full Text PDFMethylome-wide association study of different responses to risperidone in schizophrenia.
Front Pharmacol
December 2022
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
Accumulating evidence shows that DNA methylation plays a role in antipsychotic response. However, the mechanisms by which DNA methylation changes are associated with antipsychotic responses remain largely unknown. We performed a methylome-wide association study (MWAS) to evaluate the association between DNA methylation and the response to risperidone in schizophrenia.
View Article and Find Full Text PDFUnderstanding Pharmaco-Epigenomic Response of Antipsychotic Drugs Using Genome-Wide MicroRNA Expression Profile in Liver Cell Line.
Front Mol Neurosci
March 2022
Neurobiology and Genetics Division, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, India.
Interindividual variability in drug response is a major concern among patients undergoing antipsychotic drug treatment. Apart from genetic and physiological factors, this variability in drug response could also be attributed to epigenetic mechanisms. The microRNAs (miRNAs) are key epigenetic markers that play an important role in pathogenesis and drug response.
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