Neuronal function and differentiation are tightly regulated by both genome and epigenome. Based on the environmental information the epigenetic changes occur. Neurodegeneration is the consequence of dysregulation of both the genome and epigenome. In this study, we saw different types of alterations of epigenome present in neuronal cells of different model organisms for neurodegenerative disorders. The epigenetic modifications including chromatin modification, DNA methylation, and changes in regulatory RNAs (miRNA) are having a great impact on neurodegenerative disorders as well as memory. The effects of these re-editing in the neuronal cells cause Alzheimer's disease, Parkinson's disease, Huntington's disease but an unusual form of neuroepigenetics has been seen in Prion Disease. Subsequently, for the development of treatment of these diseases, epigenetic modifications should be kept in mind. Although until now many reports came on drug discovery inhibiting histone deacetylases and DNA methyltransferases to reverse the epigenetic change but they lack targeted delivery and sometimes cause a cytotoxic effect on neuronal cells. In future, advancement in targeted and non-cytotoxic drugs should be the main focus for therapeutic treatment of the neurodegenerative disorders.