The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.

Acid sphingomyelinase (ASM) is essential for the hydrolysis of sphingomyelin, leading to the production of ceramide (CE), a compound that plays a significant role in numerous physiological and pathological processes. Extensive researches have revealed the significant interactions and impacts of the ASM/CE system on numerous signaling pathways and diseases. Idiopathic inflammatory myopathies (IIM) are a distinctive group of autoimmune disorders characterized primarily by ongoing inflammation of the muscles and muscle weakness. A deeper exploration of the ASM/CE system and the mechanisms behind IIM suggests that this system may either directly or indirectly trigger the onset or enhance the process of IIM through sphingosine-1-phosphate, endoplasmic reticulum stress, immune cells, mitochondria dysfunction, reactive oxygen species, inflammatory factors and so on, which in turn stimulate pathways such as Janus kinase/signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase 1/2, interferon/STAT and so on. This indicates a concerningly broad array of connections in the pathology of IIM. This review aims to outline the potential roles of the ASM/CE system in the pathology of IIM through these extensive networks, which emphasizes the system’s promise as a target for therapy and suggesting new avenues for research in IIM.