Cd38, a transmembrane glycoprotein, can act as an enzyme with NAD-depleting and intracellular signaling activity, or as a receptor with adhesive functions [2]. It is widely expressed in various tissues and cells, especially hematopoietic cells, and plays crucial roles in immune-related processes such as cell differentiation, effector functions during inflammation, and immune-modulatory effects [2]. It is also involved in the regulation of nicotinamide adenine dinucleotide (NAD+) levels, a key molecule in many biological pathways [1,4].

Cd38 knockout mouse models have provided significant insights. In neurodegenerative diseases, Cd38 knockout mice are protected from neurodegenerative and neuroinflammatory insults, suggesting Cd38's involvement in these processes [1]. In ovarian aging, deletion of Cd38 mitigated ovarian aging, preserving fertility and follicle reserve in aged mice by countering age-related gene expression changes and intercellular communication alterations [3]. Also, in white adipose tissue and the liver during aging, the increase in Cd38 is mediated by immune cells, and ablation of senescent cells decreases Cd38, partially reversing NAD+ decline [4].

In conclusion, Cd38 is a multifunctional molecule involved in a variety of biological processes, especially in inflammation, immunity, and aging-related pathways. Gene knockout mouse models have been instrumental in revealing its role in neurodegeneration, ovarian aging, and age-related metabolic changes, providing potential therapeutic targets for these diseases.

References:

1. Guerreiro, Serge, Privat, Anne-Laure, Bressac, Laurence, Toulorge, Damien. 2020. CD38 in Neurodegeneration and Neuroinflammation. In Cells, 9, . doi:10.3390/cells9020471. https://pubmed.ncbi.nlm.nih.gov/32085567/

2. Piedra-Quintero, Zayda L, Wilson, Zachary, Nava, Porfirio, Guerau-de-Arellano, Mireia. 2020. CD38: An Immunomodulatory Molecule in Inflammation and Autoimmunity. In Frontiers in immunology, 11, 597959. doi:10.3389/fimmu.2020.597959. https://pubmed.ncbi.nlm.nih.gov/33329591/

3. Yang, Qingling, Chen, Wenhui, Cong, Luping, Wei, Chenlu, Sun, Yingpu. 2023. NADase CD38 is a key determinant of ovarian aging. In Nature aging, 4, 110-128. doi:10.1038/s43587-023-00532-9. https://pubmed.ncbi.nlm.nih.gov/38129670/

4. Chini, Claudia C S, Peclat, Thais R, Warner, Gina M, Baur, Joseph A, Chini, Eduardo N. 2020. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. In Nature metabolism, 2, 1284-1304. doi:10.1038/s42255-020-00298-z. https://pubmed.ncbi.nlm.nih.gov/33199925/