A Highly Potent Apomorphine Derivative Enhancing Neurite Outgrowth via Nrf2 Activation DOI Creative Commons
Tamaki Ishima, Hitoshi Osaka, Ryozo Nagai

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 537 - 537

Published: April 29, 2025

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related 2 (Nrf2) and exerts antioxidant effects, making it promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth (NGF) stimulation. D55, an derivative, retains the hydroxyl group at APO’s 11th position while substituting 10th with ethoxy group. D55 exhibited highest potency (EC50 = 0.5661 nM), significantly enhancing outgrowth. demonstrated efficacy (Emax ~10-fold increase), edaravone (Eda) required higher concentrations 22.5 nM) moderate effects ~4-fold increase). D30, which was replaced methoxy group, had no effect. Neurite outgrowth-promoting APO, Eda were attenuated by Nrf2 siRNA knockdown, confirming that neuroplasticity are Nrf2-mediated. These findings confirm is highly potent Nrf2-activating compound strong neuroprotective potential, providing new insights into its therapeutic applications neurodegenerative diseases associated

Language: Английский

A Highly Potent Apomorphine Derivative Enhancing Neurite Outgrowth via Nrf2 Activation DOI Creative Commons
Tamaki Ishima, Hitoshi Osaka, Ryozo Nagai

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 537 - 537

Published: April 29, 2025

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related 2 (Nrf2) and exerts antioxidant effects, making it promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth (NGF) stimulation. D55, an derivative, retains the hydroxyl group at APO’s 11th position while substituting 10th with ethoxy group. D55 exhibited highest potency (EC50 = 0.5661 nM), significantly enhancing outgrowth. demonstrated efficacy (Emax ~10-fold increase), edaravone (Eda) required higher concentrations 22.5 nM) moderate effects ~4-fold increase). D30, which was replaced methoxy group, had no effect. Neurite outgrowth-promoting APO, Eda were attenuated by Nrf2 siRNA knockdown, confirming that neuroplasticity are Nrf2-mediated. These findings confirm is highly potent Nrf2-activating compound strong neuroprotective potential, providing new insights into its therapeutic applications neurodegenerative diseases associated

Language: Английский

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