HDAC11型
小胶质细胞
组蛋白脱乙酰基酶
自噬
HDAC4型
HDAC1型
表观遗传学
组蛋白
细胞生物学
组蛋白脱乙酰酶抑制剂
HDAC6型
组蛋白脱乙酰基酶2
生物
化学
癌症研究
炎症
免疫学
生物化学
基因
细胞凋亡
作者
Soo Yeon Baek,Jeehee Lee,Taegwan Kim,Kyungmin Lee,Hoon‐Seong Choi,Hahnbeom Park,Minseob Koh,Eunha Kim,Michael E. Jung,Dimitrios Iliopoulos,Jeong‐Yeon Lee,Jonghoon Kim,Sanghee Lee
标识
DOI:10.1016/j.biopha.2023.115312
摘要
Histone deacetylases (HDACs) are key epigenetic regulators and classified into four subtypes. Despite the various roles of each HDAC isoform, the lack of selective HDAC inhibitors has limited the elucidation of their roles in biological systems. HDAC11, the sole class-IV HDAC, is highly expressed in the brain, however, the role of HDAC11 in microglia is not fully understood. Based on the modification of MC1568, we developed a novel HDAC inhibitor, 5. Interestingly, 5 suppresses lipopolysaccharide-induced microglial activation by the initiation of autophagy and subsequent inhibition of nitric oxide production. Furthermore, we demonstrated that 5 significantly alleviates depression-like behavior by inhibiting microglial activation in mouse brain. Our discovery reveals that specific pharmacological regulation of HDAC11 induces autophagy and reactive nitrogen species balance in microglia for the first time, which makes HDAC11 a new therapeutic target for depressive disorder.
科研通智能强力驱动
Strongly Powered by AbleSci AI