Emerging roles of growth differentiation factor‑15 in brain disorders (Review)

Abstract

Brain disorders, such as Alzheimer's and Parkinson's disease and cerebral stroke, are an important contributor to mortality and disability worldwide, where their pathogenesis is currently a topic of intense research. The mechanisms underlying the development of brain disorders are complex and vary widely, including aberrant protein aggregation, ischemic cell necrosis and neuronal dysfunction. Previous studies have found that the expression and function of growth differentiation factor-15 (GDF15) is closely associated with the incidence of brain disorders. GDF15 is a member of the TGFβ superfamily, which is a dimer-structured stress-response protein. The expression of GDF15 is regulated by a number of proteins upstream, including p53, early growth response-1, non-coding RNAs and hormones. In particular, GDF15 has been reported to serve an important role in regulating angiogenesis, apoptosis, lipid metabolism and inflammation. For example, GDF15 can promote angiogenesis by promoting the proliferation of human umbilical vein endothelial cells, apoptosis of prostate cancer cells and fat metabolism in fasted mice, and GDF15 can decrease the inflammatory response of lipopolysaccharide-treated mice. The present article reviews the structure and biosynthesis of GDF15, in addition to the possible roles of GDF15 in Alzheimer's disease, cerebral stroke and Parkinson's disease. The purpose of the present review is to summarize the mechanism underlying the role of GDF15 in various brain disorders, which hopes to provide evidence and guide the prevention and treatment of these debilitating conditions.

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“…It has been reported to play an important role in regulating apoptosis, inflammation, angiogenesis, and lipid metabolism, etc. in various debilitating conditions, including PD, Alzheimer's disease, Huntington's disease, and stroke [35,36]. Exogenous GDF-15 could rescue 6-OHDA-induced apoptosis of DAergic neurons both in vitro and in vivo [34].…”

Natural Products Against Renal Fibrosis via Modulation of SUMOylation

“…Recent studies found that the p53 protein participates in the pathogenesis of podocyte apoptosis (Choy Liang et al, 2021;Yang et al, 2021). As a tumor suppressor, p53 could safeguard the genome and prevent malignant transformation by halting the cell cycle and promoting apoptosis (Jiang et al, 2021;Thoms and Stark, 2021). p53 is increased under stimulation, and then upregulates the expression of pro-apoptotic genes (Eliaš and Macnamara, 2021).…”

Single nuclei RNA sequencing of the rat AP and NTS following GDF15 treatment

“…Given the anomalous scenario whereby a small subset of neurons restricted to one region of the brainstem is driving such profound effects on body weight regulation and nausea/emesis elicited by a host of disease-driven elevations in GDF15 signaling, there is an urgent need to better understand the phenotype of these neurons. As GDF15 signaling becomes increasingly linked to the progression of diseases, including cancer, obesity, cachexia, uncontrolled nausea/vomiting, and cardiovascular disease [ [22] , [23] , [24] , [25] ], understanding the transcriptomic changes elicited by GDF15 in not only GFRAL and RET-coexpressing neurons, but also the second order transcriptome alterations in other cells in the AP and NTS is imperative for the development of future therapeutics.…”