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The Role of DNA Methylation and Histone Modifications in Neurodegenerative Diseases: A Systematic Review.

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Wen, Ke-Xin 
Miliç, Jelena 
El-Khodor, Bassem 
Dhana, Klodian 
Nano, Jana 


IMPORTANCE: Epigenetic modifications of the genome, such as DNA methylation and histone modifications, have been reported to play a role in neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD). OBJECTIVE: To systematically review studies investigating epigenetic marks in AD or PD. METHODS: Eleven bibliographic databases (, Medline (Ovid), Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central, ProQuest, Lilacs, Scielo and Google Scholar) were searched until July 11th 2016 to identify relevant articles. We included all randomized controlled trials, cohort, case-control and cross-sectional studies in humans that examined associations between epigenetic marks and ND. Two independent reviewers, with a third reviewer available for disagreements, performed the abstract and full text selection. Data was extracted using a pre-designed data collection form. RESULTS: Of 6,927 searched references, 73 unique case-control studies met our inclusion criteria. Overall, 11,453 individuals were included in this systematic review (2,640 AD and 2,368 PD outcomes). There was no consistent association between global DNA methylation pattern and any ND. Studies reported epigenetic regulation of 31 genes (including cell communication, apoptosis, and neurogenesis genes in blood and brain tissue) in relation to AD and PD. Methylation at the BDNF, SORBS3 and APP genes in AD were the most consistently reported associations. Methylation of α-synuclein gene (SNCA) was also found to be associated with PD. Seven studies reported histone protein alterations in AD and PD. CONCLUSION: Many studies have investigated epigenetics and ND. Further research should include larger cohort or longitudinal studies, in order to identify clinically significant epigenetic changes. Identifying relevant epigenetic changes could lead to interventional strategies in ND.



Alzheimer Disease, Bias, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genome, Human, Histone Code, Histones, Humans, Inflammation, Neurodegenerative Diseases, Parkinson Disease, Randomized Controlled Trials as Topic

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PLoS One

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Public Library of Science (PLoS)
Medical Research Council (MR/L003120/1)
Medical Research Council (G0800270)
British Heart Foundation (None)
British Heart Foundation (None)
Medical Research Council (G0800270/1)