UNDERSTANDING THE CELLULAR LINKS BETWEEN ALLERGY, AUTOIMMUNITY, AND NEURODEGENERATION TO DEVELOP SMART ANTI-INFLAMMATORY DRUGS

Abstract

This review article aims to examine the shared mechanisms of allergic inflammation, autoimmune diseases, and neurodegenerative diseases. These three diseases have long been treated as separate entities, but it has been realized recently that they are part of a unified inflammatory response mediated by certain master regulators such as NF-KB, the inflammasome NLRP3, and the JAK/STAT pathway. The sources point to an essential change in pharmacological approaches, which is to abandon broad-spectrum immunosuppressant like corticosteroids to favor more "smart" or highly specific agents able to interfere with particular signaling pathways or to reactivate the neuro-immune conversation. The emerging therapeutic strategies include the use of monoclonal antibodies such as anti-IL-6, anti-IL-17, small kinase inhibitors like JAK, Syk, and BTK inhibitors, as well as the application of Artificial Intelligence to carry out virtual screenings to find Multi-Target Directed Ligands (MTDLs).Furthermore, the review identifies the "resolution deficit" in chronic inflammation as a critical therapeutic target, suggesting that novel drugs mimicking endogenous mediators like resolving and protecting may offer more effective cures with fewer side effects than traditional suppression. Despite all these advances, challenges persist. The process of clinical translation often faces hurdles, such as systemic toxicity, e.g., hepatotoxicity of the initial NLRP3 inhibitors, as well as the increased risk of severe infections and sepsis with blockade of cytokines In addition, the so-called "translational gap" between the efficacy of animal models and the complexity of human genetic diseases, e.g., "missing heritability" and the "two-hit model" of human disease manifestation, still persists. The review concludes that the future of anti-inflammatory medicine lies in the predictive/personalized medicine paradigms of HLA/MHC targeting and AI-assisted drug design to achieve maximum efficacy with a superior safety profile.