On October 30, 2024, Dr. Toru Miyazaki of Japan’s Institute for AIM Medicine (IAM) published an article in the multidisciplinary journal Nature Communications. The article delves into a significant lead regarding Apoptosis inhibitor of macrophage (AIM) activation that brings mankind one step closer to the possibility of finding a cure for kidney disease. The article offers vital insight into understanding how AIM can help prevent and treat diseases through its binding to IgM in the process of cleaning damaged or dead cells.
AIM plays a crucial role in removing dead cell debris (waste) from the body. AIM is generally bound to IgM, an antibody that helps defend the body against pathogens. When cells die or take damage from trauma, infection, or inflammation, AIM separates from IgM and becomes activated to begin the cleanup of waste (aforementioned dead or damaged cells). In other words, while AIM is bound to IgM, it must be released when needed in order to find and clean up dead cells.
If, for some reason, AIM remains constantly bound to IgM, this leads to a rise in the risk of developing inflammatory diseases such as acute kidney injury (AKI). Thus, a proper understanding of how AIM binds to IgM can be helpful in preventing and treating the aforementioned diseases.
The IgM antibody is composed of a constant region (Fcμ domain) and a ‘connecting bridge’ (known as a joining chain, or J chain). AIM has three head-to-tail linked SRCR domains, and among them, the cysteine in SRCR2 domain plays a critical role in the binding of AIM and IgM. The cysteine forms a powerful bond (a disulfide bond) between AIM and IgM, and raises cohesion with the J chain through electrostatic signals.
In addition, the SRCR3 domain and J chain promote the binding of AIM and IgM. In this binding, calcium serves as a lock of sorts, and the binding strength can fluctuate depending on the calcium concentration. By adjusting cysteine and calcium concentrations, it is possible to both strengthen or weaken the link and the lock and therefore manipulate the quantity of AIM activation.
Thus, while cysteine helps bind AIM to IgM, this can end up preventing AIM from being activated. A better understanding of cysteine’s role in the process can aid the development of a treatment that allows AIM to detach from IgM when needed to trigger a cleanup of dead and damaged cells more effectively.
The increased focus on AIM research in recent years has allowed experts to uncover more and more secrets behind the mechanisms of AIM activation. As more results are acquired, these discoveries will continue to accumulate and may potentially open the doors to the development of a new cure utilizing the potential of AIM. If active research in this field continues to be conducted, we may one day find a permanent solution to the threat of kidney disease for cats and humans alike.
Greycoat Research’s AIM Dr. Toru Protocol was designed based on Dr. Toru’s AIM research. AIM Dr. Toru Protocol can disrupt and weaken the binding between AIM and IgM, which allows AIM to respond to signals from dead or damaged cells more effectively and quickly begin the cleaning process.
Furthermore, the strength of the binding between AIM and IgM can be controlled through the management of calcium concentrations. AIM can help the body rid itself of waste and manage inflammation within the body to support kidney functions for a more effective method to manage feline kidney disease.