Role of intracellular signaling pathways and their inhibitors in the treatment of inflammation

• Published in: Inflammopharmacology Vol. 29; no. 3; pp. 617 - 640
• Main Authors: Nailwal, Namrata P., Doshi, Gaurav M.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2021
• Subjects: Allergology; Biomedical and Life Sciences; Biomedicine; Dermatology; Gastroenterology; Immunology; Pharmacology/Toxicology; Review; Rheumatology; Inflammation; Inhibitors; Intracellular signaling pathways; Asthma; Crohn’s disease; Ulcerative colitis
• ISSN: 0925-4692; 1568-5608
• DOI: 10.1007/s10787-021-00813-y

Inflammation is not only a defense mechanism of the innate immune system against invaders, but it is also involved in the pathogenesis of many diseases such as atherosclerosis, thrombosis, diabetes, epilepsy, and many neurodegenerative disorders. The World Health Organization (WHO) reports worldwide estimates of people (9.6% in males and 18.0% in females) aged over 60 years, suffering from symptomatic osteoarthritis, and around 339 million suffering from asthma. Other chronic inflammatory diseases, such as ulcerative colitis and Crohn’s disease are also highly prevalent. The existing anti-inflammatory agents, both non-steroidal and steroidal, are highly effective; however, their prolonged use is marred by the severity of associated side effects. A holistic approach to ensure patient compliance requires understanding the pathophysiology of inflammation and exploring new targets for drug development. In this regard, various intracellular cell signaling pathways and their signaling molecules have been identified to be associated with inflammation. Therefore, chemical inhibitors of these pathways may be potential candidates for novel anti-inflammatory drug approaches. This review focuses on the anti-inflammatory effect of these inhibitors (for JAK/STAT, MAPK, and mTOR pathways) describing their mechanism of action through literature search, current patents, and molecules under clinical trials.