ABSTRACT
Growth differentiation factor 15(GDF15) is a member of transforming growth factor β superfamily. Animal studies find that GDF15, bounding with centrally expressed receptors, reduces body weight by inhibiting food intake and by enhancing energy metabolism. In addition, GDF15 is also involved in the effects of tumor cachexia and platinum-based chemotherapy on body weight. GDF15 and its receptor could be potential targets for the treatment of such diseases.
ABSTRACT
Growth differentiation factor 15 (GDF15), a member of the transforming growth factor β (TGF-β) superfamily, is a new class of dimeric polypeptides with very low homology with other TGF-β family members. GDF15 was originally found in activated macrophages where it was secreted into the body circulation in two different cellular pathways. Moreover, GDF15 as a stress protein is widely involved in many signal pathways such as phosphoinositide 3-kinase / protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase and nuclear factor-κB, and so on, and thus involved in the regulation of various disease processes. In addition, GDF15 as a new type of stress molecule acts as a biomarker and plays a regulatory role in obesity, weight loss, cancer development, cardiovascular disease, inflammation and autoimmune diseases. Glial-derived neurotrophic factor receptor alpha-like (GFRAL) is the specific receptor of GDF15, and the molecular basis of its activity is to conduct signal transduction through GFRAL-dependent binding into multimers. The intervention of the GDF15-GFRAL signaling pathway has a great application potential in the development of weight-loss drugs and cancer prognosis recovery drugs. This review focuses on the recent progress of GDF15-GFRAL and its related signaling pathways, the molecular structure of GDF15 and GFRAL, and the mechanism of GDF15-GFRAL signaling pathway, which reveals the role and regulatory ability of GDF15 as a biomarker in the development of disease and provides new insights in potential and treatment strategies of regulating the GDF15-GFRAL signaling pathway in related diseases.