Therapeutic potency of mTOR signaling pharmacological inhibitors in the treatment of proinflammatory diseases, current status, and perspectives

Abstract

Mammalian target of rapamycin (mTOR) signaling pathway controls cell energy metabolism. There is an interplay between mTOR and proinflammatory signaling pathways, supporting the role of the pathway in the pathogenesis of inflammatory diseases. Inhibition of mTOR signaling using specific pharmacological inhibitors could offer therapeutic promise in several inflammatory-associated diseases. In this review, we summarize recent findings on the regulatory effects of mTOR signaling on inflammation and the therapeutic potency of mTOR pharmacological inhibitors in the treatment of inflammatory diseases including cancer, neurodegenerative diseases, atherosclerosis, sepsis, and rheumatoid arthritis for a better understanding and hence a better management of these diseases.

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

“…Activated AKT can cause a series of phosphorylation cascade reactions and regulate vital downstream effector molecules, like mTOR to exert its biological effect (Dirk et al, 2018;Li et al, 2019). PI3K/AKT/mTOR signaling pathway controls cell growth, proliferation, cell polarity and cytoskeleton, and EMT and angiogenesis (Peng et al, 2014;Arash and Amirhossein, 2017;Falguni et al, 2018). Recent studies have shown that activated PI3K/AKT/mTOR signaling pathway can induce EMT process, especially E-cadherin level and inhibit matrix metalloproteinases (MMPs) (Karimi et al, 2019).…”

Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application

“…On the other hand, the mTOR, a serine/threonine protein kinase, forms two complexes with distinct proteins: mTORC1 and mTORC2. These proteins are direct targets of RAPA and regulate protein synthesis; cellular proliferation, differentiation and survival; and lipid metabolism (Soltani et al, 2018). The mTORC1 composite consists mainly of mTOR, raptor, and G-protein β-subunit protein (GßL).…”

Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration

“…Rapamycin (sirolimus) is an inhibitor of mammalian target of rapamycin (mTOR). It not only blocks host pathways needed for viral replication [ 11 – 13 ], but also modulates the immune responses during infection [ 14 – 16 ]. Consequently, it may be a promising drug for treating influenza.…”

“…Previous studies suggested that mTORC2 may contribute to the regulation of apoptosis by the viral NS1 protein during infection [ 11 , 21 ]. Aberrant mTOR activation plays critical roles in the pathogenesis of proinflammatory diseases including lipopolysaccharide induced-ALI, sepsis, atherosclerosis and neurodegenerative diseases, which make mTOR an important therapeutic target for these diseases [ 14 ]. Whether mTOR activation by influenza virus contributes to pathogenesis has not yet been fully elucidated.…”