How do cytokine levels affect SMA?
Tumor Necrosis Factor- (TNF-) is a proinflammatory cytokine and activates the NFқB pathway in a biphasic manner (Ladner et al., 2003). The first transient phase is short, about one hour, while the second phase lasts for 24-36 hours. The second phase is only activated if the TNF levels are high throughout the entire period of time. This occurs during cancer cachexia which explains the constant activation of the NFB pathway. It was mentioned before that NFB transcribes its own inhibitor, IB. After its transcription, IB is transported to the nucleus and binds to NFB, which causes the complex to move back into the cytoplasm. The second phase is the more potent of the two and the major cause of muscle degradation. It is unknown how TNF activates NFB, although it may go through the aforementioned IKK pathway. It is known that TNF causes the increase in the level of MURF1 and decreases the level of MyoD mRNA, causing skeletal muscle atrophy. Ladner et al. (2003) study found that TNF alone was
