The Role of Smurf1 in Neuronal Necroptosis after Lipopolysaccharide-Induced Neuroinflammation
The role of inflammation in neurological disorders such as Alzheimer’s disease and Parkinson’s disease is gradually recognized and leads to an urgent challenge. Smad ubiquitination regulatory factor 1 (Smurf1), one member of the HECT family, is up-regulated by proinflammatory cytokines and associated with apoptosis in acute spinal cord injury. However, the function of Smurf1 through promoting neuronal necroptosis is still limited in the central nervous system (CNS). Hence, we developed a neuroinflammatory model in adult rats following lipopolysaccharide (LPS) lateral ventral injection to elaborate whether Smurf1 is involved in necroptosis in CNS injury. The up-regulation of Smurf1 detected in the rat brain cortex was similar to the necroptotic marker RIP1 expression in a time-dependent manner after LPS-induced neuroinflammation. Meanwhile, Smurf1 knockdown with siRNA inhibited neuronal necroptosis following LPS-stimulated rat pheochromocytomal PC12 cells. Thus, it was indicated that LPS-induced necroptosis could be promoted by Smurf1. In short, these studies suggest that Smurf1 might promote neuronal necroptosis after LPS-induced neuroinflammation, which might act as a novel and potential molecular target for the treatment of neuroinflammation associated diseases.
KeywordsSmad ubiquitination regulatory factor 1 Lipopolysaccharide Neuroinflammation Necroptosis Receptor-interacting protein 1 Receptor-interacting protein 3
This work was partly supported by the National Natural Science Foundation of China (Nos. 81371335, 81401013, 81401365), Nantong Science and Technology Project (MS12015056), and a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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