Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease

Escudier, Olivia; Zhang, Yunxi; Whiting, Andrew; Chazot, Paul

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease worldwide and is characterized by progressive muscle atrophy. There are currently two approved treatments, but they only relieve symptoms briefly and do not cure the disease. The main hindrance to research is the complex cause of ALS, with its pathogenesis not yet fully elucidated. Retinoids (vitamin A derivatives) appear to be essential in neuronal cells and have been implicated in ALS pathogenesis. This study explores 4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydroquinoxalin-2-yl)ethylnyl]benzoic acid (Ellorarxine, or DC645 or NVG0645), a leading synthetic retinoic acid, discussing its pharmacological mechanisms, neuroprotective properties, and relevance to ALS. The potential therapeutic effect of Ellorarxine was analyzed in vitro using the WT and SOD1G93A NSC-34 cell model of ALS at an administered concentration of 0.3–30 nM. Histological, functional, and biochemical analyses were performed. Elorarxine significantly increased MAP2 expression and neurite length, increased AMPA receptor GluA2 expression and raised intracellular Ca2+ baseline, increased level of excitability, and reduced Ca2+ spike during depolarization in neurites. Ellorarxine also displayed both antioxidant and anti-inflammatory effects. Overall, these results suggest Ellorarxine shows relevance and promise as a novel therapeutic strategy for treatment of ALS.

Citation

Escudier, O., Zhang, Y., Whiting, A., & Chazot, P. (2024). Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease. International Journal of Molecular Sciences, 25(18), Article 9764. https://doi.org/10.3390/ijms25189764

• Journal Article Type: Article
• Acceptance Date: Sep 7, 2024
• Online Publication Date: Sep 10, 2024
• Publication Date: Sep 2, 2024
• Deposit Date: Oct 25, 2024
• Publicly Available Date: Oct 25, 2024
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 18
• Article Number: 9764
• DOI: https://doi.org/10.3390/ijms25189764
• Keywords: neurodegeneration, Ellorarxine, DC645, neuroprotective effects, Amyotrophic lateral sclerosis, neuroinflammation, retinoid
• Public URL: https://durham-repository.worktribe.com/output/2955039