ABSTRACT
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a soluble endoplasmic reticulum (ER) luminal protein and its expression and secretion can be induced by ER stress. Despite initially being classified as a neurotrophic factor, MANF has been demonstrated to have restorative and protective effects in many different cell types such as neurons, liver cells, retinal cells, cardiac myocytes, and pancreatic ß cells. However, underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the understanding of the trophic activities of MANF in tissue repair and regeneration as well as underlying molecular mechanisms. The structural motifs and immune modulation of MANF are also described. We therefore propose that MANF might be a promising therapeutic target for tissue repair.
Subject(s)
Astrocytes , Nerve Growth Factors , Astrocytes/metabolism , Nerve Growth Factors/metabolism , Neurons , Myocytes, Cardiac/metabolism , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum StressABSTRACT
The NLRP3 inflammasome is a multiprotein binding compound comprising NLRP3, connector protein ASC, and effector protein pro-caspase-1. When the NLRP3 inflammasome senses a danger signal from the host or pathogen, activated caspase-1 cleaves the precursors of interleukin (IL)-1ß and IL-18 into mature proinflammatory cytokines, simultaneously causing lysis via the pore-forming protein gasdermin D. This induction of cell inflammatory pyroptosis suggests that it is a key process in the innate immune response to pathogens or cellular stress. Recent studies have shown that NLRP3 inflammasome also plays an important role in regulating autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosclerotic cholangitis. In this review, we summarize the structure, activation and modulation of the NLRP3 inflammasome, highlight the progress in research on the role of NLRP3 inflammasome in the occurrence and development of autoimmune liver diseases, and discuss potential strategies for targeting the NLRP3 inflammasome in the treatment of autoimmune liver diseases.
