Potentiation of Nerve Growth Factor-Induced Neurite Outgrowth by Fluvoxamine: Role of Sigma-1 Receptors, IP3 Receptors and Cellular Signaling Pathways

NGF binding to cell-surface TrkA receptor results in activated receptor complexes, which contain adaptors such as SHC (SH2-containing protein), GRB2 (growth-factor-receptor bound protein 2) and Gab (GRB2-associated binding) proteins. These proteins recruit the protein SOS, increasing Ras-guanosine triphosphate (Ras-GTP) levels by catalyzing nucleotide exchange on Ras. Ras also activates the PI3K-PDK1 (3-phosphoinosisitide-dependent protein kinase 1)- Akt pathway. The activation of TrkA by NGF leads to activation of multiple signaling pathways, including PLC-γ, PI3K, p38MAPK, and JNK signaling pathways and Ras/Raf/MEK/ERK/MAPK pathways. The activation of sigma-1 receptors on the endoplasmic reticulum (ER) by sigma-1 receptor agonists (e.g., SA4503 and fluvoxamine) might interact with IP3 receptors on the ER. Ca2+ released by the interaction between sigma-1 receptors and IP3 receptors may play a role in the potentiation of NGF-induced neurite outgrowth in PC12 cells. Subsequently, several signaling pathways are implicated in the potentiation of NGF-induced neurite outgrowth by sigma-1 receptor agonists.

Publication

Potentiation of Nerve Growth Factor-Induced Neurite Outgrowth by Fluvoxamine: Role of Sigma-1 Receptors, IP3 Receptors and Cellular Signaling Pathways. (2008) Tomoko Nishimura, et al. PLoS One. 2008;3(7):e2558. Figure: F8. All organisms Drosophila melanogaster Homo sapiens

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