Pharmacological insights into autophagy modulation in autoimmune diseases

Abstract

As a cellular bulk degradation and survival mechanism, autophagy is implicated in diverse biological processes. Genome-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), indicating that autophagy dysregulation may be involved in the development of autoimmune diseases. A series of autophagy modulators have displayed protective effects on autoimmune disease models, highlighting the emerging role of autophagy modulators in treating autoimmune diseases. This review explores the roles of autophagy in the autoimmune diseases, with emphasis on four major autoimmune diseases [SLE, rheumatoid arthritis (RA), IBD, and experimental autoimmune encephalomyelitis (EAE)]. More importantly, the therapeutic potentials of small molecular autophagy modulators (including autophagy inducers and inhibitors) on autoimmune diseases are comprehensively analyzed.

Curcumin ameliorates H2O2‑induced inflammatory response in chondrocytes by inducing autophagy activation

“…Various previous studies have reported that autophagy is constitutively active in chondrocytes (26,27). Appropriate autophagy has a housekeeping role in preventing diseases such as cancer, cardiomyopathy, diabetes, liver diseases and autoimmune diseases, as well as neurodegeneration and infections (28)(29)(30)(31)(32)(33)(34). It is a well-conserved mechanism and has been confirmed to be important in various physical events.…”

Postoperative Ileus with the Topical Application of Tongfu Decoction Based on Network Pharmacology and Experimental Validation

“…The comprehensive and systematic analysis of drugs-active-ingredients-target proteins in network pharmacology conforms to the holistic concept, and its research concept coincides with the overall concept of TCM syndrome differentiation and treatment. Network pharmacology is often used in the study of TCM components and targets [ 32 – 37 ], especially TCM compound prescriptions. Different chemical components in TCM compounds may have synergistic effects in terms of reducing toxicity.…”

Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

“…ULK1 also activates autophagy by phosphorylation of downstream proteins to participate in the regulation of some stress mechanisms. Excepted for lapidating LC3B and driving the formation of autophagosomes, ATG16L1 is also a direct ULK1 target and regulated by ULK1 phosphorylation at Ser278 during stress 153 . In addition, based on proteomic methods combined with experimental methods, it was found that ULK1 phosphorylated SEC16A at Ser846, promoting the assembling COPII components in ERES, and regulating the transport of ER to the Golgi apparatus 154 .…”

“…In lung inflammation and even acute lung injury under influenza A virus infection, lacking of HIF-1 α decreases glycolysis levels and promotes autophagy through the AMPK α /ULK1 pathway to promote IAV copy 252 . Moreover, under infectious conditions, ULK1 kinase, can directly phosphorylate ATG16L1, and phosphorylated ATG16L1 localizes to the site of internalizing bacteria and promotes antimicrobial autophagy, a process implicated in Crohn's disease, and the mechanism remains to be investigated 153 .…”