Histone demethylases in neurodevelopment and neurodegenerative diseases.

ABSTRACT

Neurodevelopment can be precisely regulated by epigenetic mechanisms, including DNA methylations, noncoding RNAs, and histone modifications. Histone methylation was a reversible modification, catalyzed by histone methyltransferases and demethylases. So far, dozens of histone lysine demethylases (KDMs) have been discovered, and they (members from KDM1 to KDM7 family) are important for neurodevelopment by regulating cellular processes, such as chromatin structure and gene transcription. The role of KDM5C and KDM7B in neural development is particularly important, and mutations in both genes are frequently found in human X-linked mental retardation (XLMR). Functional disorders of specific KDMs, such as KDM1A can lead to the development of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Several KDMs can serve as potential therapeutic targets in the treatment of neurodegenerative diseases. At present, the function of KDMs in neurodegenerative diseases is not fully understood, so more comprehensive and profound studies are needed. Here, the role and mechanism of histone demethylases were summarized in neurodevelopment, and the potential of them was introduced in the treatment of neurodegenerative diseases.