Pycard, also known as PYD and CARD domain containing or ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), is a pivotal adaptor protein in inflammasome assembly and activation. It contributes to innate immunity and is involved in pathways such as NOD-like receptor signaling pathway [2]. It plays an essential role in the pathogenesis of multiple diseases including tendinopathy, chronic obstructive pulmonary disease (COPD), atherosclerosis, restenosis, rheumatoid arthritis, and psoriasis [1,2,3,4,5].

In a tendinopathy study, pristimerin alleviated the disease by promoting the autophagic degradation of AIM2-PYCARD/ASC complex, enhancing the K63-linked ubiquitin chains of PYCARD/ASC [1]. In Pycard-deficient mice, miRNA maturation was inhibited, and neointima formation was prevented as Pycard deficiency promoted chaperone-mediated autophagic degradation of AGO2 in adipose tissue [3]. In COPD, PYCARD was identified as a crucial PANoptosis-related gene, positively related to NOD-like receptor signaling pathway and promoting immune cell infiltration [2].

In conclusion, Pycard is a key adaptor protein in inflammasome activation with a significant impact on innate immunity. Gene-knockout mouse models, such as the Pycard-deficient mice, have revealed its role in multiple disease-related biological processes, including miRNA biogenesis, neointima formation, and immune cell infiltration in tendinopathy, atherosclerosis-related diseases, and COPD respectively [1,2,3].

References:

1. Jiang, Huaji, Xie, Yingchao, Lu, Jiansen, Gong, Xiaoqian, Yu, Xiao. 2023. Pristimerin suppresses AIM2 inflammasome by modulating AIM2-PYCARD/ASC stability via selective autophagy to alleviate tendinopathy. In Autophagy, 20, 76-93. doi:10.1080/15548627.2023.2249392. https://pubmed.ncbi.nlm.nih.gov/37647255/

2. Shi, Rui, Liang, Renwen, Wang, Fang, Chen, Alex F, Yang, Weimin. 2024. Identification and experimental validation of PYCARD as a crucial PANoptosis-related gene for immune response and inflammation in COPD. In Apoptosis : an international journal on programmed cell death, 29, 2091-2107. doi:10.1007/s10495-024-01961-6. https://pubmed.ncbi.nlm.nih.gov/38652339/

3. Li, Jian, Yao, Hongmin, Zhao, Fujie, Zou, Ming-Hui, Xie, Zhonglin. 2023. Pycard deficiency inhibits microRNA maturation and prevents neointima formation by promoting chaperone-mediated autophagic degradation of AGO2/argonaute 2 in adipose tissue. In Autophagy, 20, 629-644. doi:10.1080/15548627.2023.2277610. https://pubmed.ncbi.nlm.nih.gov/37963060/

4. Geng, Xue-Li, Jiang, Yong-Sen, Zhao, Chun-Nan, Liu, Yan-Ling, Ding, Pei-Jian. 2024. Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients. In European journal of medical research, 29, 218. doi:10.1186/s40001-024-01813-8. https://pubmed.ncbi.nlm.nih.gov/38576041/

5. Xu, Bingyang, Yu, Biao, Xu, Zining, Wu, Na, Wu, Jiawen. 2024. Investigation and Confirmation of PYCARD as a Potential Biomarker for the Management of Psoriasis Disease. In Journal of inflammation research, 17, 6415-6437. doi:10.2147/JIR.S468746. https://pubmed.ncbi.nlm.nih.gov/39310902/