Ncor1, also known as Nuclear receptor corepressor 1, is a transcriptional corepressor that links chromatin-modifying enzymes with gene-specific transcription factors. It plays a crucial role in various biological processes, including metabolism, immune response, and cell development, by regulating gene expression. It is involved in pathways such as glycolysis, fatty acid oxidation, and the regulation of transcription factors like PPARα [2,4]. Genetic models, especially KO/CKO mouse models, have been instrumental in understanding its functions.

In dendritic cells, Ncor1 ablation generates immune-tolerant DCs through enhanced glycolysis and oxidative phosphorylation, supported by fatty acid oxidation-driven oxygen consumption. Inhibiting key elements in these metabolic pathways disrupts the immunological tolerance transcriptional signature [1]. In vascular smooth muscle cells, smooth muscle Ncor1 deficiency leads to a switch from a contractile to a degradative phenotype, increasing the incidence of aortic aneurysms [3]. In myeloid cells, Ncor1 depletion exacerbates Mycobacterium tuberculosis growth by dysregulating the AMPK-mTOR-TFEB axis [7]. In osteoclastogenesis, Ncor1 deficiency promotes osteoclast and neutrophil formation, exacerbating periodontitis [5]. In endothelial cells, depletion of Ncor1 increases angiogenic capacity by altering Notch signaling [6].

In summary, Ncor1 is essential for maintaining normal physiological functions in multiple cell types. KO/CKO mouse models have revealed its role in diseases such as aortic aneurysm, periodontitis, and Mycobacterium tuberculosis infection. Understanding Ncor1 function can provide potential therapeutic targets for these and other related diseases.

References:

1. Sen, Kaushik, Pati, Rashmirekha, Jha, Atimukta, Nanda, Ranjan Kumar, Raghav, Sunil K. 2022. NCoR1 controls immune tolerance in conventional dendritic cells by fine-tuning glycolysis and fatty acid oxidation. In Redox biology, 59, 102575. doi:10.1016/j.redox.2022.102575. https://pubmed.ncbi.nlm.nih.gov/36565644/

2. Müller, Lena, Hainberger, Daniela, Stolz, Valentina, Ellmeier, Wilfried. 2018. NCOR1-a new player on the field of T cell development. In Journal of leukocyte biology, 104, 1061-1068. doi:10.1002/JLB.1RI0418-168R. https://pubmed.ncbi.nlm.nih.gov/30117609/

3. Du, Lin-Juan, Sun, Jian-Yong, Zhang, Wu-Chang, Jia, Feng, Duan, Sheng-Zhong. 2022. NCOR1 maintains the homeostasis of vascular smooth muscle cells and protects against aortic aneurysm. In Cell death and differentiation, 30, 618-631. doi:10.1038/s41418-022-01065-1. https://pubmed.ncbi.nlm.nih.gov/36151473/

4. Paluvai, Harikrishnareddy, Shanmukha, Kumar D, Tyedmers, Jens, Backs, Johannes. 2023. Insights into the function of HDAC3 and NCoR1/NCoR2 co-repressor complex in metabolic diseases. In Frontiers in molecular biosciences, 10, 1190094. doi:10.3389/fmolb.2023.1190094. https://pubmed.ncbi.nlm.nih.gov/37674539/

5. Ma, X X, Meng, X Q, Wang, Y L, Duan, S Z, Lu, H X. 2022. Ncor1 Deficiency Promotes Osteoclastogenesis and Exacerbates Periodontitis. In Journal of dental research, 102, 72-81. doi:10.1177/00220345221116927. https://pubmed.ncbi.nlm.nih.gov/35983582/

6. Teichmann, Tom, Malacarne, Pedro, Zehr, Simonida, Warwick, Timothy, Brandes, Ralf P. 2024. NCoR1 limits angiogenic capacity by altering Notch signaling. In Journal of molecular and cellular cardiology, 188, 65-78. doi:10.1016/j.yjmcc.2024.02.003. https://pubmed.ncbi.nlm.nih.gov/38359551/

7. Biswas, Viplov Kumar, Sen, Kaushik, Ahad, Abdul, Gupta, Bhawna, Raghav, Sunil Kumar. 2023. NCoR1 controls Mycobacterium tuberculosis growth in myeloid cells by regulating the AMPK-mTOR-TFEB axis. In PLoS biology, 21, e3002231. doi:10.1371/journal.pbio.3002231. https://pubmed.ncbi.nlm.nih.gov/37590294/