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Facilitatory Roles of Novel Compounds Designed from Cyclopentenone Prostaglandins on Neurite Outgrowth-Promoting Activities of Nerve Growth Factor by Takumi Satoh; Kyoji Furuta; Keiichiro Tomokiyo; Daisaku Nakatsuka; Motoki Tanikawa; Makoto Nakanishi; Maki Miura; Shuuitsu Tanaka; Tetsuro Koike; Hiroshi Hatanaka; Kazuyoshi Ikuta; Masaaki Suzuki; Yasuyoshi Watanabe is a Neuroscience article available to read on EtoBox.

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**Abstract:** Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the G~1~ phase in vitro and to suppress tumor growth in vivo. However, their effects on neurons are unclear. Here, we report that some cyclopentenone PGs function as neurite outgrowth‐promoting factors. They promoted neurite outgrowth from PC12 cells and from dorsal root ganglion explants but only in the presence of nerve growth factor (NGF). We refer to these PGs as neurite outgrowth‐promoting PGs (NEPPs). Through study of the structure‐function relationship of NEPP1‐10 and related compounds, we found that the cross‐conjugated dienone moiety of NEPPs was essential for promoting neurite outgrowth, and NEPP10 was concluded to be the best candidate for drug development. We also investigated the intracellular mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin heavy chain binding protein/glucose‐regulated protein 78 (BiP/GRP78) plays a role in the promotion, based on the following observations: Antisense nucleotides for BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein level increased in response to NEPPs; and overexpression of BiP/GRP78 protein

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Author

Takumi Satoh; Kyoji Furuta; Keiichiro Tomokiyo; Daisaku Nakatsuka; Motoki Tanikawa; Makoto Nakanishi; Maki Miura; Shuuitsu Tanaka; Tetsuro Koike; Hiroshi Hatanaka; Kazuyoshi Ikuta; Masaaki Suzuki; Yasuyoshi Watanabe

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0022-3042)

Published

2002

Language

EN

Field

Neuroscience (Life Sciences)