Psmb8, also known as proteasome subunit β8, is one of the immunoproteasome catalytic subunits, playing a key role in protein homeostasis. It is involved in multiple biological processes and is associated with pathways like inflammation, immune response, and mitochondrial regulation. Genetic models, such as knockout (KO) mice, have been crucial in studying its functions [1].

In myocardial ischemia/reperfusion (I/R) injury, cardiomyocyte-specific Psmb8 overexpression in mice ameliorated I/R-mediated cardiac injury and dysfunction by reducing mitochondrial division via downregulating Drp1, while Psmb8 knockout mice showed the opposite effects [1]. In the context of manganese-induced neurotoxicity, inhibition of Psmb8 mitigated neuroinflammation, improved recognition memory, and alleviated synapse deficits in Mn-treated mice [4]. Psmb8 also has implications in diseases like Parkinson's disease, where its upregulation in peripheral blood mononuclear cells and post-mortem brains was observed [2]. In viral infections, like porcine respiratory and reproductive syndrome virus (PRRSV), Psmb8 promoted the virus infection by degrading IRF3, and knockdown of Psmb8 inhibited PRRSV replication [3].

In conclusion, Psmb8 is essential in maintaining protein homeostasis and is involved in various biological processes related to inflammation, mitochondrial function, and immune response. Studies using KO mouse models have revealed its significance in multiple disease areas, including cardiac I/R injury, manganese-induced neurotoxicity, Parkinson's disease, and viral infections, providing valuable insights into potential therapeutic strategies.

References:

1. Su, Hui-Xiang, Xu, Luo-Luo, Li, Pang-Bo, Jiang, Wen-Xi, Li, Hui-Hua. 2024. Psmb8 inhibits mitochondrial fission and alleviates myocardial ischaemia/reperfusion injury by targeting Drp1 degradation. In Cell death & disease, 15, 803. doi:10.1038/s41419-024-07189-1. https://pubmed.ncbi.nlm.nih.gov/39516219/

2. Nguyen, Huu Dat, Kim, Young Eun, Nhat Nguyen, Linh Thi, Pham, Hong Ngoc, Ma, Hyeo-Il. 2023. Upregulation of immunoproteasome PSMB8 is associated with Parkinson's disease. In Parkinsonism & related disorders, 114, 105797. doi:10.1016/j.parkreldis.2023.105797. https://pubmed.ncbi.nlm.nih.gov/37562243/

3. Li, Sihan, Guo, Shuyuan, Liu, Fang, Zhu, Yingqi, Feng, Wen-Hai. 2024. miR-451-targeted PSMB8 promotes PRRSV infection by degrading IRF3. In Journal of virology, 98, e0078424. doi:10.1128/jvi.00784-24. https://pubmed.ncbi.nlm.nih.gov/39194214/

4. Guo, Tingting, Liu, Chunyan, Yang, Changhao, Su, Peng, Chen, Jingyuan. 2022. Immunoproteasome subunit PSMB8 regulates microglia-mediated neuroinflammation upon manganese exposure by PERK signaling. In Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 163, 112951. doi:10.1016/j.fct.2022.112951. https://pubmed.ncbi.nlm.nih.gov/35378207/