Epigenetics of Alzheimer's disease and frontotemporal dementia - PubMed (original) (raw)

Review

Epigenetics of Alzheimer's disease and frontotemporal dementia

Chendhore S Veerappan et al. Neurotherapeutics. 2013 Oct.

Abstract

This article will review the recent advances in the understanding of the role of epigenetic modifications and the promise of future epigenetic therapy in neurodegenerative dementias, including Alzheimer's disease and frontotemporal dementia.

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Fig. 1

Fig. 1

The general overview of neurodegeneration and possible avenues for epigenetic therapy. Histone methylation/acetylation levels along with 5-methylcytosine and 5-hydroxymethylcystosine levels undergo age-related epigenetic drift and potentially deregulate genes associated with neurodegeneration. Mutations in epigenetic readers, writers and erasers have been implicated in multiple neurological disorders including cognitive decline. Cellular stress, toxicity and altered SAM levels are associated with altered promoter DNA methylation in risk-associated genes. Noncoding RNAs (ncRNAs) are associated with the regulation of neurodegeneration and neurotropic genes and were found to be differentially regulated in disease models. Together, an altered epigenetic landscape due to deregulation or mutations in epigenetic readers, writers and erasers is being portrayed in AD and FTD. Studies have shown several possible epigenetic therapy intervention avenues. Specific HDACi have been shown to be beneficial in restoring cognitive decline and memory formation in disease models due to important the role of histone acetylation in maintaining neuronal plasticity. DNMTi (and potentially TET inhibitors), may epigenetically restore expression of specific genes dysregulated in neurodegeneration. Similarly, the anti-mRNA and/or anti-lncRNA could be used to target deregulated ncRNAs that alter expression of epigenetic and neurodegenerative factors

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