DNA methylation in brain diseases involving cognitive deficits

Finally, although this topic has been reviewed extensively previously (Day, Kennedy, & Sweatt, 2015; Day & Sweatt, 2012; Graff & Tsai, 2013), there is a strong link between DNA modifications and cognitive disease states. In addition to the classical case of Rett syndrome (a neurodevelopmental disability caused by mutations in the X-linked DNA methylation reader methyl-CpG-binding protein 2) (Amir et al., 1999), alterations in DNA methylation pathways have been implicated in Fragile X syndrome (Sutcliffe et al., 1992), Alzheimer disease (Coppieters et al., 2013; De Jager et al., 2014), frontotemporal dementia (Liu et al., 2014), and age-associated cognitive decline (Oliveira, Hemstedt, & Bading, 2012). In some cases, DNA methylation states can serve as nongenetic markers of disease state or prognosis, enabling potential use as disease biomarkers (De Jager et al., 2014; Liu et al., 2014). In addition, there is growing interest in the potential use of DNA methylation-targeted therapeutics for cognitive disease states (Day et al., 2015; Day & Roberson, 2015), although much further research and exploration are required to translate our current understanding of DNA modifications in memory to clinical settings.

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