Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration

Cell & Bioscience

Review

Caixia Guo¹  Hongmei Liu²  Tie-Shan Tang³  Dongfang Jiang⁴  Tingting Li⁴ 

[1] Beijing Institute of Genomics, Chinese Academy of Sciences/China National Center for Bioinformation, 100101, Beijing, China;Chinese Academy of Sciences, University of Chinese Academy of Sciences, 100101, Beijing, China;State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;Beijing Institute for Stem Cell and Regenerative Medicine, 100101, Beijing, China;State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;Beijing Institute for Stem Cell and Regenerative Medicine, 100101, Beijing, China;Chinese Academy of Sciences, University of Chinese Academy of Sciences, 100101, Beijing, China;State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China;Chinese Academy of Sciences, University of Chinese Academy of Sciences, 100101, Beijing, China;

关键词: Chromatin remodeling;    Small molecules;    Epigenomics;    Histone modifications;    Neurodevelopment;    Neurodegenerative diseases;   

DOI  :  10.1186/s13578-023-00953-4

 received in 2022-09-22, accepted in 2023-01-03,  发布年份 2023

来源: Springer

【 摘 要 】

The dynamic changes in chromatin conformation alter the organization and structure of the genome and further regulate gene transcription. Basically, the chromatin structure is controlled by reversible, enzyme-catalyzed covalent modifications to chromatin components and by noncovalent ATP-dependent modifications via chromatin remodeling complexes, including switch/sucrose nonfermentable (SWI/SNF), inositol-requiring 80 (INO80), imitation switch (ISWI) and chromodomain-helicase DNA-binding protein (CHD) complexes. Recent studies have shown that chromatin remodeling is essential in different stages of postnatal and adult neurogenesis. Chromatin deregulation, which leads to defects in epigenetic gene regulation and further pathological gene expression programs, often causes a wide range of pathologies. This review first gives an overview of the regulatory mechanisms of chromatin remodeling. We then focus mainly on discussing the physiological functions of chromatin remodeling, particularly histone and DNA modifications and the four classes of ATP-dependent chromatin-remodeling enzymes, in the central and peripheral nervous systems under healthy and pathological conditions, that is, in neurodegenerative disorders. Finally, we provide an update on the development of potent and selective small molecule modulators targeting various chromatin-modifying proteins commonly associated with neurodegenerative diseases and their potential clinical applications.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

Fig. 6

Fig. 8

Fig. 3

Fig. 49

Fig. 4

Fig. 7

Fig. 4

Fig. 6

Fig. 2

Fig. 5

Fig. 1

Fig. 4

Fig. 2

Fig. 5

Fig. 3

Fig. 5

41116_2022_35_Article_IEq659.gif

41116_2022_35_Article_IEq655.gif

Fig. 47

Fig. 2

41116_2022_35_Article_IEq649.gif

Fig. 1

41116_2022_35_Article_IEq645.gif

41116_2022_35_Article_IEq598.gif

41116_2022_35_Article_IEq591.gif

41116_2022_35_Article_IEq563.gif