Soo Yeon Baek Hee, Lee Jee Kim, Taegwan Lee, Hyelim Choi, Hoon-Seong Park, Hahnbeom Koh, Minseob Kim, Eunha Jung, Michael E. Iliopoulos, Dimitrios Lee, Jeong-Yeon Kim, Jonghoon Lee, Sang hee 2024-01-12T06:33:43Z 2024-01-12T06:33:43Z 2023-09-19 2023-10 0753-3322 https://pubs.kist.re.kr/handle/201004/79811 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. English Elsevier Masson Development of a novel histone deacetylase inhibitor unveils the role of HDAC11 in alleviating depression by inhibition of microglial activation Article 10.1016/j.biopha.2023.115312 1 Biomedicine & Pharmacotherapy, v.166 Biomedicine & Pharmacotherapy 166 Y scie scopus 001063387900001 Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Pharmacology & Pharmacy HDAC inhibitor Microglial activation Neuroinflammation Depressive disorder