Interpreting crosstalk between TNF-α and NGF: potential implications for disease

Tumour necrosis factor-α (TNF-α) is a proinflammatory cytokine, whereas nerve growth factor (NGF) is a neurotrophin that can promote neural cell survival, differentiation and maturation. However, recent papers indicate that TNF-α has a pivotal role in fate decisions of neural cells in normal noninflammatory conditions, whereas NGF contributes to maintenance of inflammation. Although these observations suggest a close relationship between NGF and TNF-α signalling, crosstalk between these factors is not fully understood. In this Opinion article, we review recent reports regarding possible crosstalk between NGF and TNF-α and we propose a positive-feedback loop of their expression. We discuss the possible mechanisms by which disturbance of the crosstalk could contribute to diseases such as cancer and Alzheimer's disease.