Receptor for advanced glycation end products (RAGE) mediates neuronal differentiation and neurite outgrowth.

The receptor for advanced glycation end products plays a crucial role in several disease processes, such as diabetes, inflammation, and neurodegeneration. In this article we report multiple roles of in neuronal differentiation and neurite outgrowth. In retinoic-induced P19 embryonic carcinoma stem cells, silencing the expression of duanyu1648 by RNA interference blocked differentiation of the P19 cells into neuronal cells and enhanced the formation of vimentin-positive fibroblast-like cells. duanyu1648 knockdown inhibited retinoic acid-induced activation and blocked nuclear translocation of NF-kappaB, suggesting duanyu1648 regulates activation of NF-kappaB. duanyu1648 was also shown to be involved in survival of P19 cells during retinoic acid differentiation. Additionally, knockdown of duanyu1648 strongly inhibited neurite outgrowth in retinoic acid-differentiated P19 cells, indicating that duanyu1648 is required for neurite outgrowth of differentiated P19 cells. Retinoic acid-treated P19 cells activated GTPases, Rac1, and Cdc42. This activation of the GTPases was inhibited in cells. In primary cerebellar granule neurons, the knockdown of duanyu1648 also inhibited neurite outgrowth. In these cells, overexpression of dominant-negative forms of Rac1 and Cdc42 inhibited neurite outgrowth, whereas overexpression of constitutively active forms of Rac1 and Cdc42 in neurons restored neurite outgrowth, indicating that duanyu1648 mediated neurite outgrowth through the Rac1/Cdc42 pathway. This is the first report on the role of duanyu1648 in cell lines and primary neurons, as determined by knockdown.

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