The Epigenetics Changes in Parkinson's Disease: a Novel Therapeutic Target

• Published in: CNS neuroscience & therapeutics Vol. 20; no. 4; pp. 299 - 300
• Main Authors: Yuan, Ti‐Fei, Li, Jiang, Shan, Chun‐Lei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2014; John Wiley and Sons Inc
• Subjects: Acetylation; Animal models; Apoptosis; Apoptosis - drug effects; Binding sites; Biomarkers; Brain; Conflicts of interest; Deoxyribonucleic acid; DNA; DNA methylation; Dopamine; Epigenetics; Family medical history; Gene expression; Genomes; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Human subjects; Humans; Hydroxamic Acids - pharmacology; Lymphocytes; Mitochondria; Mitochondria - drug effects; Movement disorders; MPP; MPTP Poisoning - drug therapy; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neuroprotective Agents - pharmacology; Neurotoxicity; Parkin protein; Parkinson's disease; Parkinsons disease; Pathogenesis; Plasticity; Proteins; Synuclein; Therapeutic applications
• ISSN: 1755-5930; 1755-5949; 1755-5949
• DOI: 10.1111/cns.12245

In recent years, the epigenetic changes have been well recognized and documented in brain development, plastic changes, as well as different brain diseases, including the PD. With an animal model (overexpression of α‐synuclein in fly) of PD, the histone deacetylase (HDAC) inhibitor was firstly found to inhibit synuclein toxicity to the dopamine neuron , followed by a series of studies that established the importance of histone acetylation in pathogenesis of PD . In a recent paper appearing on CNS Neuroscience & Therapeutics, Zhu et al. , the authors found that the application of HDAC inhibitor is able to block the mitochondrial fragmentation, which is an early event during MPP+ induced neuronal apoptosis. Epigenetic changes related to Parkinson's disease The associated gene, DNA methylation, Histone acetylation, Regulating miRNAs SNCA (α‐synuclein) Reduced [Jowaed et al. 2010] Inhibited [Outeiro et al. 2007] Decreased [Junn et al. 2009; Doxakis 2010] Parkin No change [Cai et al. 2011; De Mena L et al. 2013] – – UCHL‐1 No change [Barrachina and Ferrer 2009] – – MAPT No change [Barrachina and Ferrer 2009] – – TNFA (TNF‐α) Unclear [Pieper et al. 2008] – – PARK16–1q32, GPNMB, and STX1B, Altered [IPDGC, 2011] – – – – – Altered expression of miRNAs in lymphocytes of PD patients [Margis et al., 2011] – – – miR‐133b decreased [Kim et al. 2007] – – – miR34b decreased [Minones‐Moyano et al. 2011] Present investigations on epigenetic changes of PD patients largely rely on post‐mortem brain analyses, therefore lacking evidences of progressive changes, and it is hard to differentiate if the changes are resulted from the previous therapeutic treatments. [...]the authors identified lists of genes with either increased or decreased DNA methylation in PD patients from brain and blood samples, showing highly correlated variations in both samples.