Epigenetic Dysregulation
Image by NHGRI, NIHEpigenetics refers to heritable changes in gene expression or phenotype that occur without changes to the DNA sequence and can provide an additional mechanism for regulating gene transcription. These additional controls are mainly conveyed as DNA methylation and histone modifications, regulated by DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). Targeting these mechanisms has been suggested as a possible therapeutic strategy (Egger et al., 2004; Hahnen et al., 2008).
Whether disturbance of epigenetic processes can lead to PD remains unclear. Apparent differences in the methylation state of the TNFalpha gene promoter have been reported in brains of people with PD (Pieper et al., 2008). Alpha-synuclein has also been shown to bind directly to histones, where it appears to reduce acetylation (Kontopoulos et al., 2006).
Reference:
Egger G, Liang G, Aparicio A, Jones PA. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 2004;429(6990):457-63.
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Kontopoulos E, Parvin JD, Feany MB. Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet. 2006;15(20):3012-23.
Pieper HC, Evert BO, Kaut O, Riederer PF, Waha A, Wüllner U. Different methylation of the TNF-alpha promoter in cortex and substantia nigra: Implications for selective neuronal vulnerability. Neurobiol Dis. 2008;32(3):521-7.
Hahnen E, Hauke J, Tränkle C, Eyüpoglu IY, Wirth B, Blümcke I. Histone deacetylase inhibitors: possible implications for neurodegenerative disorders. Expert opinion on investigational drugs. 2008;17(2):169-84.
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