Abstract
Simple SummaryDNA methylation is an epigenetic modification of genes which affects corresponding gene expression. During the developmental stage, embryonic stem cells undergo various epigenetic modifications to produce different specialized cells. DNA methylation appears as one of the important epigenetic modifications which not only potentiate neuronal development but also have been sought in various neurodegenerative diseases, such as Alzheimer’s disease. The present work focuses on the history of DNA methylation, its role in neurodevelopment functions, and how assessment of DNA hypermethylation and hypomethylation can be utilized for the prognosis of AD and other neurodegenerative diseases. This review also paves the way for the development of novel treatment strategies based on targeting DNA methylation in neurodegenerative diseases.DNA methylation, in the mammalian genome, is an epigenetic modification that involves the transfer of a methyl group on the C5 position of cytosine to derive 5-methylcytosine. The role of DNA methylation in the development of the nervous system and the progression of neurodegenerative diseases such as Alzheimer’s disease has been an interesting research area. Furthermore, mutations altering DNA methylation affect neurodevelopmental functions and may cause the progression of several neurodegenerative diseases. Epigenetic modifications in neurodegenerative diseases are widely studied in different populations to uncover the plausible mechanisms contributing to the development and progression of the disease and detect novel biomarkers for early prognosis and future pharmacotherapeutic targets. In this manuscript, we summarize the association of DNA methylation with the pathogenesis of the most common neurodegenerative diseases, such as, Alzheimer’s disease, Parkinson’s disease, Huntington diseases, and amyotrophic lateral sclerosis, and discuss the potential of DNA methylation as a potential biomarker and therapeutic tool for neurogenerative diseases.
Highlights
Epigenetic modification refers to heritable changes in gene expression that are not encoded by the DNA sequence [1]
RG108 blocks the methylation in motor neurons and causes improvement in disease [177]. This review summarizes those epigenetic modifications that are responsible for many genes’ functions in the body
DNA methylation influences the pathophysiology of age-related disease, aging, and dementia [179,180], Modifications in chromatin organization, transcriptional changes, and a variety of neurological illnesses and diseases are all linked to abnormal methylation changes [181]
Summary
Epigenetic modification refers to heritable changes in gene expression that are not encoded by the DNA sequence [1]. DNA methylation is an inherent epigenetic process in which DNA methyltransferases move a CH3 group covalently to the C-5 of the cytosine ring of DNA [2]. DNA methyltransferases and epigenetic modification such as methylation in DNA may participate in new functions in the brain [9]. This is more common in species with heavy DNA methylation patterns. A heritable mechanism for controlling gene expression is a covalent alteration in the genome and proteins present in histone, which is mainly present in chromatin. Histone ends are exposed to an amount of covalent alteration such as acetylation, methylation, phosphorylation, ubiquitination, and sumoylation, all of which control key cellular processes including gene transcription, replication, as well as repair [12]. Even though 50% of CpG islands have established transcription start sites, they are frequently vacant of common promoter essentials such as TATA boxes [18]
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